Health Care Professional Information
Bachelor’s button, featherfew, Santa Maria, wild chamomile, wild quinine
Feverfew is a plant that belongs to the family Compositeae. It is widely used in traditional medicine for the treatment of fevers, migraine headaches, rheumatoid arthritis, stomach ache, toothache, insect bites and infertility.
Although much of its activity is attributed to the active compound parthenolide, a parthenolide-free extract of feverfew demonstrated free radical-scavenging properties, affording protection against UV-induced sun damage (3). Feverfew extracts also possess antiprotozoal properties (2).
In clinical trials a feverfew extract reduced the frequency of migraine attacks (1) and a feverfew/ginger formulation prevented mild headache before the onset of moderate to severe headache in patients with migraine (16). In another study, a combination of feverfew and acupuncture treatments led to greater improvements in quality of life in women with migraine, compared to feverfew or acupuncture alone (19).
Feverfew also demonstrated anticancer effects in vitro (4) (5) (6) (17) (18). A Phase I clinical study involving cancer patients showed that up to 4 mg of parthenolide was well tolerated; however, parthenolide could not be detected in the plasma (7).
More studies are warranted.
- Migraine prophylaxis
- Sesquiterpene lactones: Parthenolide, artecanin, artemorin, balchanin, canin, costunolide, 10-epicanin, epoxyartemorin, 1-beta-hydroxyarbusculin, 3-beta-hydroxycostunolide, 8-alpha-hydroxyestagiatin, 8-beta hydroxyreynosinn, 3-beta-hydroxyparthenolide, manolialide, reynosin, santamarine, epoxysantamarine, secotanaparthenolide A, secotanaparthenolide B, tanaparthin-alpha-peroxide, and 3,4-beta-epoxy-8-deoxycumambrin B
- Volatile oils: Camphor, camphene, p-cymene, and bornyl acetate
- Flavonoids: 6-hydroxykaempferol 3,6-dimethyl ether, 6-hydroxykaempferol 3,6,4′-trimethyl ether (tanetin), quercetagetin 3,6-dimethyl ether, quercetagetin 3,6,3′-trimethyl ether (accompanied by isomeric 3,6,4′-trimethyl ether), quercetin, apigenin (also apigenin 7-glucuronide), luteolin (also luteolin 7-glucuronide), chrysoeriol, santin, jaceidin, and centaureidin
Mechanism of Action
The sesquiterpene lactones, particularly parthenolide, are the active ingredients and are responsible for feverfew's beneficial effects; parthenolide attenuates activation of the NF-kappa B complex to block transcription of inflammatory proteins (12). In glioblastoma cells, parthenolide induces caspase 3/7-mediated apoptosis independent of NF-kappa B suppression (13). It is believed that all the feverfew constituents have a synergistic effect in preventing migraines. Some researchers believe that the flavonol content also has anti-inflammatory effects (8) (9).
Parthenolide sensitizes the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) leading to apoptosis via activation of both caspases 8 and 3 in hepatocellular carcinoma cells (18).
Individuals allergic to ragweed, chrysanthemums, marigolds, or other members of the Compositae family may have cross-sensitivity to feverfew.
Common: Minor gastrointestinal distress; oral ulcerations may result from chewing fresh feverfew leaves; airborne contact dermatitis has been reported (10); exacerbated dermatitis was also observed following use of a moisturizer containing feverfew (20).
Withdrawal symptoms: Muscle stiffness, anxiety, and moderate pain usually occur following cessation of long-term feverfew use (post-feverfew syndrome). (8)
Cytochrome P450 3A4 substrates: Feverfew inhibits CYP1A2/2C8/2C9/2C19/2D6 and 3A4, and can affect the intracellular concentration of drugs metabolized by these enzymes (15).
Literature Summary and Critique
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- Diener HC, Pfaffenrath V, Schnitker J, Friede M, Henneicke-von Zepelin HH. 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. Nov 2005;25(11):1031-1041.
- Izumi E, Morello LG, Ueda-Nakamura T, et al. Trypanosoma cruzi: antiprotozoal activity of parthenolide obtained from Tanacetum parthenium (L.) Schultz Bip. (Asteraceae, Compositae) against epimastigote and amastigote forms. Exp Parasitol. Mar 2008;118(3):324-330.
- Martin K, Sur R, Liebel F, et al. Parthenolide-depleted Feverfew (Tanacetum parthenium) protects skin from UV irradiation and external aggression. Arch Dermatol Res. Feb 2008;300(2):69-80.
- Yip-Schneider MT, Nakshatri H, Sweeney CJ, Marshall MS, Wiebke EA, Schmidt CM. Parthenolide and sulindac cooperate to mediate growth suppression and inhibit the nuclear factor-kappa B pathway in pancreatic carcinoma cells. Mol Cancer Ther. Apr 2005;4(4):587-594.
- Zhang S, Ong CN, Shen HM. Involvement of proapoptotic Bcl-2 family members in parthenolide-induced mitochondrial dysfunction and apoptosis. Cancer Lett. Aug 10 2004;211(2):175-188.
- Parada-Turska J, Paduch R, Majdan M, Kandefer-Szerszen M, Rzeski W. Antiproliferative activity of parthenolide against three human cancer cell lines and human umbilical vein endothelial cells. Pharmacol Rep. Mar-Apr 2007;59(2):233-237.
- Curry EA, 3rd, Murry DJ, Yoder C, et al. Phase I dose escalation trial of feverfew with standardized doses of parthenolide in patients with cancer.Invest New Drugs. Aug 2004;22(3):299-305.
- Johnson ES, Kadam NP, Hylands DM, Hylands PJ. Efficacy of feverfew as prophylactic treatment of migraine. Br Med J (Clin Res Ed). Aug 31 1985;291(6495):569-573.
- Williams CA, Hoult JR, Harborne JB, Greenham J, Eagles J. A biologically active lipophilic flavonol from Tanacetum parthenium. Phytochemistry. Jan 1995;38(1):267-270.
- Paulsen E, Christensen LP, Andersen KE. Compositae dermatitis from airborne parthenolide. Br J Dermatol. Mar 2007;156(3):510-515.
- Phytotherapy ESCo. ESCOP Monographs on the medicinal uses of plant drugs. Exeter, London; March 1996.
- Reuter U, Chiarugi A, Bolay H, Moskowitz MA. Nuclear factor-kappaB as a molecular target for migraine therapy. Ann Neurol. Apr 2002;51(4):507-516.
- Anderson KN, Bejcek BE. Parthenolide induces apoptosis in glioblastomas without affecting NF-kappaB. J Pharmacol Sci. Feb 2008;106(2):318-320.
- Murphy JJ, Heptinstall S, Mitchell JR. Randomised double-blind placebo-controlled trial of feverfew in migraine prevention. Lancet. Jul 23 1988;2(8604):189-192.
- Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom. 2004;18(19):2273-81.
- Cady RK, Goldstein J, Nett R, Mitchell R, Beach ME, Browning R. A double-blind placebo-controlled pilot study of sublingual feverfew and ginger (LipiGesic™ M) in the treatment of migraine.Headache. 2011 Jul-Aug;51(7):1078-86.
- 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.2010 Feb;20(1):21-34.
- Carlisi D, Anneo A, Angileri L, et al. Parthenolide sensitizes hepatocellular carcinoma cells to TRAIL by inducing the expression of death receptors through inhibition of STAT3 activation.J Cell Physiol.2011 Jun;226(6):1632-41.
- Ferro EC, Biagini AP, da Silva ÍE, Silva ML, Silva JR. The combined effect of acupuncture and Tanacetum parthenium on quality of life in women with headache: randomised study. Acupunct Med. 2012 Dec;30(4):252-7.
- Killoran CE, Crawford GH, Pedvis-Leftick A. Two cases of compositae dermatitis exacerbated by moisturizer containing feverfew. Dermatitis. 2007 Dec;18(4):225-9.
- Pareek A, Suthar M, Rathore GS, Bansal V. Feverfew (Tanacetum parthenium L.): A systematic review. Pharmacogn Rev. 2011 Jan;5(9):103-10.
How It Works
Bottom Line: Feverfew may benefit patients with migraine headaches.
One or more compounds found in feverfew are thought to prevent migraines. One such compound, parthenolide, was found to block the formation of inflammatory proteins in a recent laboratory study. A feverfew extract was shown to reduce the number of migraine attacks and also decrease the mild headache that occurs before a migraine attack.
Feverfew also showed anticancer effects in lab studies. Human studies are needed.
- To prevent migraine headaches
Some clinical trials support this use. Post-feverfew withdrawal syndrome (consisting of muscle stiffness, anxiety, headaches, nausea, and vomiting) can occur after patients discontinue using this herb.
- To treat arthritis
Although compounds in feverfew show anti-inflammatory activity in the laboratory, clinical trials do not support this use.
- To relieve painful and heavy menstruation
No scientific evidence supports this use.
- To treat psoriasis
Although compounds in feverfew show anti-inflammatory activity in the laboratory, but human data are lacking.
- To treat protozoal diseases
One laboratory study found that feverfew could stop the growth of the protozoa that causes Chagas disease.
- To treat sun damage
Feverfew protected against UV-induced sun damage in a laboratory study.
One hundred and seventy patients with migraine were randomized to receive 6.25 mg feverfew CO2-extract or placebo three times a day for 16 weeks following a baseline period of 4 weeks. Results showed that the frequency of migraines decreased by 1.9 attacks in the treatment group and by 1.3 attacks in those on placebo from 4.79 attacks per month. This difference was found to be statistically significant. The feverfew extract was well tolerated with nonspecific adverse effects that were seen in the placebo group as well. Researchers conclude that feverfew is effective in reducing the frequency of migraine attacks in patients.
- Stomach upset, contact dermatitis
- Mouth ulcerations may result from chewing fresh feverfew leaves.
- Post-feverfew syndrome: Withdrawal symptoms often develop when patients stop taking feverfew after a long period of time. These include muscle stiffness, anxiety, moderate pain, headache, nausea, and vomiting.
Last updated: May 20, 2014