Articles

Feverfew

Plant Part Used

Leaf

Active Constituents

Sesquiterpene lactones (mainly parthenolide), tannins, and camphor. (1)

[span class=alert]This section is a list of chemical entities identified in this dietary supplement to possess pharmacological activity. This list does not imply that other, yet unidentified, constituents do not influence the pharmacological activity of this dietary supplement nor does it imply that any one constituent possesses greater influence on the overall pharmacological effect of this dietary supplement.[/span]

Introduction

Feverfew has gained immense popularity because of its prophylactic effectiveness in relieving migraine headaches.(2) It may take up to a month for therapeutic results to be seen. Once it is discontinued the effectiveness for migraine prevention dissipates. Feverfew is also used for inflammatory conditions such as rheumatoid arthritis,(3) relaxing smooth muscle in the uterus,(4) inhibiting platelet aggregation and blood clotting(5),(6) and fever.(7) The flowers from the plant have been used as a vermifuge. Feverfew has also been used as a natural insecticide.(8)

Interactions and Depletions

Interactions

Dosage Info

Dosage Range

100-250mg (standardized extract), 1-3 times a day.

Fresh Leaf: 1 to 3 leaves (25 to 75 mg), 1-2 times daily has been recommended.(2),(9)

Most Common Dosage

250mg (standardized extract) daily.

Fresh Leaf: 1 leaf (25 mg), 1-2 times daily has been recommended.

Standardization

[span class=doc]Standardization represents the complete body of information and controls that serve to enhance the batch to batch consistency of a botanical product, including but not limited to the presence of a marker compound at a defined level or within a defined range.[/span]

The most current available medical and scientific literature indicates that this dietary supplement should be standardized to 0.2% parthenolide per dose. Canada's Health Protection Branch has supported the use of a proprietary and authenticated Tanacetum parthenium product containing at least 0.2% parthenolide for the prevention of migraines.(10)

Uses

Frequently Reported Uses

  • Migraine Headache Prevention

Other Reported Uses

  • Inflammation
  • Rheumatoid Arthritis
  • Vermifuge

Toxicities & Precautions

General

No toxicity has been seen in clinical trials in recommended doses.(11)

Abruptly discontinuing use may create a reflex response with migraines.(12)

Allergy

Do not use if allergic to pyrethrums. Use with caution in individuals with severe ragweed allergy or allergy to members of the daisy and chrysanthemum family (Compositae).(13),(29)

Health Conditions

Based on pharmacology, use with caution in individuals with bleeding disorders.(14)

Pregnancy/ Breast Feeding

Based on pharmacology and animal studies, do not use if pregnant.(11)

Age Limitations

Do not use in children under 2 years of age unless recommended by a physician.

Pharmacology

Feverfew reportedly inhibits the manufacture of inflammatory mediators such as leukotrienes, prostaglandins and thromboxanes.(15),(16) Feverfew may influence the initial stages of the inflammation process in contrast to the action of aspirin and nonsteroidal anti-inflammatory drugs (NSAID).(17),(18) Clinical trials in the treatment of rheumatoid arthritis have been inconclusive. Authors have speculated that a higher dosage of feverfew is needed to interfere with arachidonate-mediated inflammation.(15)

Parthenolide, isolated from feverfew leaves, was reported in laboratory studies to inhibit the pro-inflammatory signaling pathway in inflammatory processes.(19) Parthenolide was reported to directly bind to IkB kinase b (IKKb), the kinase subunit reported to play a critical role in cytokine mediated inflammation.

Several clinical studies have reported the efficacy of feverfew in the prevention of migraine headaches.(20),(21),(22),(30) Feverfew exhibits several pharmacological actions that may be implicated in migraine prophylaxis, including inhibition of histamine secretion,(23) inhibition of granular secretion, platelet aggregation and arachidonate mediated responses,(6),(24) and inhibition of vascular smooth muscle contractility.(25) Also, excess serotonin (5HT) release from platelets has been implicated as one of the primary mechanisms in the pathogenesis of migraines, which may explain some of feverfew’s prophylactic activity in migraine headaches.(26) Feverfew extracts have also been reported to have GABA activity in a laboratory study.(31)

A systematic review of the literature supporting the use of feverfew in migraine prevention have been performed.(27) The authors report that the clinical effectiveness of feverfew in the prevention of migraine has not been established beyond a reasonable doubt and more research needs to be performed.

Parthenolide has also been reported to inhibit proliferation and kills various cancer cells mainly by inducing apoptosis through caspase 3/7 without suppression of NF-kappaB activity.(32),(33)

References

  1. Bohlmann F, et al. Sesquiterpene Lactones and Other Constituents from Tanacetum parthenium. Phytochemistry. 1982;21:2543-49.
  2. View Abstract: Johnson ES, et al. Efficacy of Feverfew as Prophylactic Treatment of Migraine. British Medical Journal. 1985;291:569-73.
  3. Makheja AM, et al. The Active Principle in Feverfew. Lancet. 1981;2(8254):1054.
  4. Groenewegen WA, et al. Amounts of Feverfew in Common Preparations of the Herb. Lancet. 1986; 1(8471):44-45.
  5. Biggs MJ, et al. Platelet Aggregation in Patients Using Feverfew for Migraine. Lancet. 1982;2(8301):776.
  6. View Abstract: Groenewegen WA, et al. A Comparison of the Effects of an Extract of Feverfew and Parthenolide, a Component of Feverfew, on Human Platelet Activity In-vitro. J Pharm Pharmacol. 1990;42(8):553-57.
  7. View Abstract: Sumner H, et al. Inhibition of 5-Lipoxygenase and Cyclo-oxygenase in Leukocytes by Feverfew. Biochem Pharmacol. 1992;43(11):2313-20.
  8. Dreisbach RH. Handbook of Poisoning. 11th ed. CA: Lange Medical Publications; 1983:552.
  9. View Abstract: O’Hara M, Kiefer D, Farrell K, Kemper K. A review of 12 commonly used medicinal herbs. Arch Fam Med. Sep1998;7(6):523-536.
  10. Drug Identification Number Notification. Drugs Directorate, Therapeutic Products Division, Health Protection Branch, Health Canada. Ottawa, Canada.
  11. Newall CA, et al. Herbal Medicines: A Guide for Health Care Professionals. London: The Pharmaceutical Press; 1996:119-21.
  12. PDR for Herbal Medicines, 2nd ed. Montvale, NJ: Medical Economics Company; 2000:307.
  13. Schmidt RJ. Plant dermatitis. Compasitae. Clin Dermatol. Apr1986;4(2):46-61.
  14. View Abstract: Heck AM, et al. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm. Jul2000;57(13): 1221-7.
  15. View Abstract: Pattrick M, et al. Feverfew in Rheumatoid Arthritis: A Double-blind, Placebo Controlled Study. Ann Rheum Dis. 1989;48:547-49.
  16. View Abstract: Makheja AM, et al. A Platelet Phospholipase Inhibitor from the Medicinal Herb Feverfew (Tanacetum parthenium). Prostaglandin Leukotri Med. 1982;8:653-60.
  17. View Abstract: Jain NK, Kulkarni SK. Antinociceptive and Anti-inflammatory Effects of Tanacetum parthenium L. Extract in Mice and Rats. J Ethnopharmacol. Dec1999;68(1-3):251-9.
  18. View Abstract: Williams CA, Harborne JB, Geiger H, et al. The Flavonoids of Tanacetum parthenium and T. vulgare and Their Anti-inflammatory Properties. Phytochemistry. Jun1999;51(3):417-23.
  19. Kwok BHB, Koh B, Ndubuisi MI, et al. The anti-inflammatory natural product parthenolide from the medicinal herb feverfew, directly binds to and inhibits IkB kinase. Chemistry and Biology. 2001;114:1-8.
  20. View Abstract: Murphy JJ, et al. Randomised Double-blind Placebo-controlled Trial of Feverfew in Migraine Prevention. Lancet. 1988;2(8604):189-92.
  21. View Abstract: Prusinski A, Durko A, Niczyporuk-Turek A. [Feverfew as a Prophylactic Treatment of Migraine]. Neurol Neurochir Pol. 1999;33(Suppl 5):89-95.
  22. Palevitch D, et al. Feverfew as a Prophylactic Treatment for Migraine: A Double-Blind Placebo Controlled Study. Phytotherapy Research. 1997;11:508-11.
  23. View Abstract: Hayes NA, et al. The Activity of Compounds Extracted from Feverfew on Histamine Release from Rat Mast Cells. J Pharm Pharmacol. Jun1987;39(6):466-70.
  24. View Abstract: Capasso F. The Effect of An Aqueous Extract of Tanacetum parthenium L. on Arachidonic Acid Metabolism by Rat Peritoneal Leucocytes. J Pharm Pharmacol. Jan1986;38(1):71-72.
  25. View Abstract: Barsby RW, et al. Feverfew Extracts and Parthenolide Irreversibly Inhibit Vascular Responses of the Rabbit Aorta. J Pharm Pharmacol. Sep1992;44(9):737-40.
  26. View Abstract: Bejar E. Parthenolide Inhibits the Contractile Responses of Rat Stomach Fundus to Fenfluramine and Dextroamphetamine but not Serotonin. J Ethnopharmacol. Jan1996;50(1):1-12.
  27. View Abstract: Pittler MH, Vogler BK, Ernst E. Feverfew for Preventing Migraine (Cochrane Review). Cochrane Database Syst Rev. 2000;(3):CD002286
  28. Wu C, Chen F, Wang X, Wu Y, Dong M, He G, Galyean RD, He L, Huang G. Identification of antioxidant phenolic compounds in feverfew (Tanacetum parthenium) by HPLC-ESI-MS/MS and NMR. Phytochem Anal. Sep 2007;18(5):401-410.
  29. Sharma VK, Sethuraman G. Parthenium dermatitis. Dermatitis. Dec 2007;18(4):183-190. Review.
  30. Shrivastava R, Pechadre JC, John GW. Tanacetum parthenium and Salix alba (Mig-RL) combination in migraine prophylaxis: a prospective, open-label study. Clin Drug Investig. 2006;26(5):287-296.
  31. Jäger AK, Krydsfeldt K, Rasmussen HB. Bioassay-guided isolation of apigenin with GABA-benzodiazepine activity from Tanacetum parthenium. Phytother Res. Nov 2009;23(11):1642-1644.
  32. Lesiak K, Koprowska K, Zalesna I, Nejc D, Düchler M, Czyz M. Parthenolide, a sesquiterpene lactone from the medical herb feverfew, shows anticancer activity against human melanoma cells in vitro. Melanoma Res. Feb 2010;20(1):21-34.
  33. Anderson KN, Bejcek BE. Parthenolide induces apoptosis in glioblastomas without affecting NF-kappaB.J Pharmacol Sci. Feb 2008;106(2):318-320. Epub 2008 Feb 15.