Chapter 126 Tanacetum parthenium (Feverfew)
Tanacetum parthenium (family: Asteraceae)
Synonym: Chrysanthemum parthenium
Common names: feverfew, featherfew
General Description
Chemical Composition
The major active chemicals in the plant have been hypothesized to be sesquiterpene lactones, principally parthenolide. However, many investigators have found evidence of other active constituents, including both lipophilic compounds (like sesquiterpene lactones) and hydrophilic compounds, although their exact identity has not been determined.1–3 The flowering herb also contains 0.02% to 0.07% volatile oils (L-camphor, L-borneol, terpenes, and miscellaneous esters).4,5 Various compounds in the volatile oil have shown pharmacologic activity.6
History and Folk Use
Feverfew has been used for centuries as a febrifuge and for the treatment of migraines and arthritis. Other historic uses of feverfew have been in the treatment of anemia, earache, dysmenorrhea, dyspepsia, trauma, and intestinal parasites.4 It has also been used as an abortifacient and in gardens to control noxious pests (its pyrethrin component is an effective insecticide and herbicide).
Pharmacology
Feverfew has demonstrated some remarkable pharmacologic effects in experimental studies. Extracts of feverfew have been shown to inhibit the synthesis of compounds that promote inflammation, including inflammatory prostaglandins, leukotrienes, and thromboxanes. No adverse effects reported for feverfew mimic those of aspirin or nonsteroidal antiinflammatory drugs (NSAIDs), suggesting that the effects of feverfew are in some way distinct from those of the drugs. Inhibition of phospholipase A2 is more like the effects of corticosteroids.7
Feverfew also has favorable effects on the behavior of blood platelets in vitro,7,8 including inhibition of platelet aggregation and the secretion of inflammatory and allergic mediators like histamine and serotonin. Parthenolide components also exert a tonic effect on vascular smooth muscle.9
Clinical Applications
Feverfew has been used for centuries to relieve fever, migraines, and arthritis. The only condition with confirmed scientific documentation at present is in the prevention and treatment of migraine headache.
Migraine Headache
Physician John Hill, in his book The Family Herbal (1772), noted, “In the worst headache this herb exceeds whatever else is known.” A 1983 survey found that 70% of 270 migraine sufferers who had eaten feverfew daily for prolonged periods claimed that the herb decreased the frequency and/or intensity of their attacks.10 Many of these patients had shown no response to orthodox medicines.
Numerous double-blind trials have been conducted on the efficacy of feverfew in migraine patients,10–15 the results of which have been assessed in three meta-analyses.16–18 The first two of these concluded that the majority of studies show that feverfew extracts are superior to placebo for decreasing the frequency and severity of migraine headaches, although most of the studies were of relatively low methodologic quality, and efficacy was not proved beyond a reasonable doubt.14,17 The third meta-analysis concluded that feverfew extracts have not been proved in controlled trials to prevent migraine better than placebo.18
One double-blind, randomized clinical trial compared the effects of a combination of a feverfew extract (100 mg) with riboflavin 400 mg and magnesium 300 mg taken daily with riboflavin 25 mg.19 The control, riboflavin 25 mg, appeared to be just as active as the combination formula, and the trial showed that combining feverfew and magnesium with riboflavin adds no additional benefits for preventing migraine headaches.
In an open trial, feverfew combined with Salix alba (white willow) extracts, 300 mg of each twice a day, has been shown effective at preventing and reducing the severity of migraine without aura.20 A combination of Zingiber officinale (ginger) and feverfew was effective in an open trial for relieving acute migraine pain.21 It is not clear if either extract is superior to feverfew alone, and double-blind randomized trials are necessary.
Rheumatoid Arthritis
Inflammatory compounds released by white blood cells and platelets contribute greatly to the inflammation and cellular damage found in rheumatoid arthritis. Inhibition of the release of inflammatory particles by feverfew is much greater than that achieved by NSAIDs like aspirin.8 This finding, coupled with many of feverfew’s other effects, indicates that feverfew can reduce inflammation in rheumatoid arthritis.
Although a double-blind, placebo-controlled study demonstrated no apparent benefit from oral feverfew in rheumatoid arthritis, the dosage used was small (76 mg dried powdered feverfew leaf, corresponding to two medium-sized leaves), the level of parthenolide was not determined in the product, and patients continued to take NSAIDs, a practice that has been suggested to reduce the efficacy of feverfew.22 Therefore, the benefit of feverfew in rheumatoid arthritis has not yet been determined.
Dosage
The effectiveness of feverfew was thought to depend on adequate levels of parthenolide, although multiple studies confirm that there are multiple active compounds in feverfew and that parthenolide-free extracts are still active.23,24 It is difficult to determine the relevance of measuring parthenolide in extracts; assessments of activity of extracts would perhaps be superior although more expensive.
The preparations used in some successful clinical trials had a parthenolide content of 0.4% to 0.66%. The dosage of feverfew used in the London Migraine Clinic study was one capsule containing 25 mg of the freeze-dried pulverized leaves given twice a day.6 In the Nottingham study it was one capsule containing 82 mg of dried powdered leaves given once a day.7 Therefore, the daily dosage of parthenolide that may be effective in preventing a migraine headache is roughly 0.25 to 0.5 mg.
Toxicity
There were no reports of toxic reactions in patients taking feverfew in the 6-month migraine study. Feverfew has been used by large numbers of people for many years without reports of toxicity. Chewing the leaves, however, may result in aphthous ulcerations, and some sensitive persons experience an exudative dermatitis from external contact.25 In clinical trials, neither mouth ulcers nor dermatitis was more common in the feverfew groups than the placebo groups; in one trial, aphthous ulcers were actually more common in the placebo group.12
1. Brown A.M.G., Edwards C.M., Davey M.R., et al. Pharmacological activity of feverfew (Tanacetum parthenium (L) Schultz-Bip.): assessment by inhibition of human polymorphonuclear leukocyte chemiluminescence in-vitro. J Pharm Pharmacol. 1997;49:558–561.
2. Sumner H., Salan U., Knight D.W., et al. Inhibition of 5-lipoxygenase and cyclo-oxygenase in leukocytes by feverfew: involvement of sesquiterpene lactones and other components. Biochem Pharmacol. 1992;43:2313–2320.
3. Marles R.J., Kaminski J., Arnason J.T., et al. A bioassay for inhibition of serotonin release from bovine platelets. J Nat Prod. 1992;55:1044–1056.
4. Duke J.A. CRC handbook of medicinal herbs. Boca Raton, FL: CRC Press; 1985. 118
5. Bohlmann F., Zdero C. Sesquiterpene lactones and other constituents from Tanacetum parthenium. Phytochemistry. 1982;21:2543–2549.
6. Pugh W.J., Sambo K. Prostaglandin synthetase inhibitors in feverfew. J Pharm Pharmacol. 1988;40:743–745.
7. Makheja A.N., Bailey J.M. A platelet phospholipase inhibitor from the medicinal herb feverfew (Tanacetum parthenium). Prostaglandins Leukot Med. 1982;8:653–660.
8. Heptinstall S., White A., Williamson L., et al. Extracts of feverfew inhibit granule secretion in blood platelets and polymorphonuclear leukocytes. Lancet. 1985;1:1071–1074.
9. Barsby R.W., Salan U., Knight D.W., et al. Feverfew and vascular smooth muscle: extracts from fresh and dried plants show opposing pharmacological profiles, dependent upon sesquiterpene lactone content. Planta Med. 1993;59:20–25.
10. Johnson E.S., Kadam N.P., Hylands D.M., et al. Efficacy of feverfew as prophylactic treatment of migraine. Br Med J (Clin Res Ed). 1985;291:569–573.
11. Diener H.C., Pfaffenrath V., Schnitker J., et al. Efficacy and safety of 6.25 mg t.i.d. feverfew CO2-extract (MIG-99) in migraine prevention-a randomized, double-blind, multicentre, placebo-controlled study. Cephalalgia. 2005;25(11):1031–1041.
12. Murphy J.J., Heptinstall S., Mitchell J.R.A. Randomized double-blind placebo-controlled trial of feverfew in migraine prevention. Lancet. 1988;2:189–192.
13. Palevitch D., Earon G., Carasso R. Feverfew (Tanacetum parthenium) as a prophylactic treatment for migraine: a double-blind placebo-controlled study. Phytother Res. 1997;11:508–511.
14. De Weerdt C.J., Bootsma H.P.R., Hendriks H. Herbal medicine in migraine prevention. Randomized double-blind placebo-controlled crossover trial of a feverfew preparation. Phytomedicine. 1996;3:225–230.
15. Kuritzky A., Elhacham Y., Yerushalmi Z., et al. Feverfew in the treatment of migraine: its effect on serotonin uptake and platelet activity. Neurology. 1994;44(Suppl 2):293P.
16. Pittler M.H., Vogler B.K., Ernst E. Feverfew for preventing migraine. Cochrane Database Syst Rev. 2000:CD002286.
17. Vogler B.K., Pittler M.H., Ernst E. Feverfew as a preventive treatment for migraine: a systematic review. Cephalalgia. 1998;18:704–708.
18. Pittler M.H., Ernst E. Feverfew for preventing migraine. Cochrane Database Syst Rev, 2004;1:CD002286.
19. Maizels M., Blumenfeld A., Burchette R. A combination of riboflavin, magnesium, and feverfew for migraine prophylaxis: a randomized trial. Headache. 2004;44:885–890.
20. Shrivastava R., Pechadre J.C., John G.W. Tanacetum parthenium and Salix alba (Mig-RL) combination in migraine prophylaxis: a prospective, open-label study. Clin Drug Invest. 2006;26(5):287–296.
21. Cady R.K., Schreiber C.P., Beach M.E., et al. Gelstat Migraine (sublingually administered feverfew and ginger compound) for acute treatment of migraine when administered during the mild pain phase. Med Sci Monit. 2005;11(9):PI65–PI69.
22. Pattrick M., Heptinstall S., Doherty M. Feverfew in rheumatoid arthritis: a double blind, placebo controlled study. Ann Rheum Dis. 1989;48:547–549.
23. Sur R., Martin K., Liebel F., et al. Anti-inflammatory activity of parthenolide-depleted feverfew (Tanacetum parthenium). Inflammopharmacology. 2009;17(1):42–49.
24. Sumner H., Salan U., Knight D.W., et al. Inhibition of 5-lipoxygenase and cyclo-oxygenase in leukocytes by feverfew. Involvement of sesquiterpene lactones and other components. Biochem Pharmacol. 1992;43(11):2313–2320.
