Feverfew

Purported Benefits, Side Effects & More

Feverfew

Purported Benefits, Side Effects & More
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Feverfew

Common Names

  • Featherfew
  • Santa Maria
  • wild chamomile
  • wild quinine

For Patients & Caregivers

Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.


What is it?

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. 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.

What are the potential uses and benefits?
  • To prevent migraine headaches

    A few studies 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, a clinical trial did 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, human data are lacking.

 

What are the side effects?
  • Stomach upset
  • Red, itchy rash
  • Mouth ulcerations when chewing fresh feverfew leaves
  • Withdrawal symptoms (post-feverfew syndrome): May occur when patients stop taking feverfew after a long period of time. These include muscle stiffness, anxiety, moderate pain, headache, nausea, and vomiting.
What else do I need to know?

Do Not Take if:

You are allergic to ragweed, chrysanthemums, marigolds, or other members of the Compositae family.

You are taking Cytochrome P450 3A4 substrate drugs: Feverfew may increase the risk of side effects of these drugs. Clinical relevance is not known.

You are taking anticoagulant/antiplatelet drugs: Feverfew may increase the risk of bleeding. Clinical relevance is not known.

For Healthcare Professionals

Scientific Name
Tanacetum parthenium
Clinical Summary

Feverfew is a plant that belongs to the daisy/sunflower family. 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 compound parthenolide, a parthenolide-free extract of feverfew demonstrated free radical-scavenging properties, affording protection against UV-induced sun damage (1). Feverfew extracts also possess antiprotozoal (2), antibacterial (3), anti-inflammatory (1) (4), and antioxidant (5) properties.

In clinical studies, a feverfew extract reduced the frequency of migraine attacks (6); a formulation containing feverfew was reported useful in decreasing the duration of aura (33); and a feverfew/ginger formula prevented mild headache before the onset of moderate to severe headache in patients with migraine (7). In another study, a combination of feverfew and acupuncture treatments led to greater improvements in quality of life in women with migraine, compared with feverfew or acupuncture alone (8). A systematic review found the overall evidence of efficacy for migraine to be mixed, citing the need for high-quality research (35).
In another study, feverfew did not benefit patients with rheumatoid arthritis (9).

In addition, parthenolide demonstrated anticancer effects in vitro (10) (11) (12) (13) (14) (15) (16) (17). A phase I clinical study involving cancer patients showed that up to 4 mg of parthenolide was well tolerated; however, it could not be detected in the plasma (18). Consequently, a synthetic analog dimethylamino-parthenolide (DMAPT), a more hydrophilic form of parthenolide, with greater bioavailability was identified. Oral administration of DMAPT has been found to be safe, and resulted in increased plasma concentrations in an animal model (19). More studies are warranted.

Purported Uses and Benefits
  • Migraine
  • Arthritis
  • Dysmenorrhea
  • Psoriasis
Mechanism of Action

The sesquiterpene lactones, particularly parthenolide, are the active constituents responsible for feverfew’s beneficial effects. Parthenolide attenuates activation of the NF-kappa B complex to block transcription of inflammatory proteins (21). The inhibition of this pathway also leads to decreased platelet activity (22). Other mechanisms that produce antiplatelet activity by parthenolide include sulfhydryl group alterations, changes in protein kinase C interactions, and arachidonic acid metabolism (22) (23) (24). The flavonol content also has anti-inflammatory effects (25) (26).

In vitro studies suggest various activities induced by parthenolide can produce antiproliferative effects. In colorectal cancer cells, it suppresses angiogenesis by reducing VEGF and VEGF-receptor expression. (10) In cervical and breast cancer cell lines, parthenolide modulates apoptosis-regulating gene expression (11) and activates both apoptosis pathway and AMPK-autophagy survival pathway through ROS generation (12). In glioblastoma cells, it induces caspase 3/7-mediated apoptosis independent of NF-kappa B suppression (27). 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 (17).

Contraindications

Individuals allergic to ragweed, chrysanthemums, marigolds, or other members of the Compositae family may have cross-sensitivity to feverfew.

Adverse Reactions

Common: Minor gastrointestinal distress; oral ulcerations from chewing fresh feverfew leaves; contact dermatitis (28) (34); and exacerbated dermatitis following use of a moisturizer containing feverfew (29).

Withdrawal symptoms: Muscle stiffness, anxiety, and moderate pain usually occur following cessation of long-term use of feverfew (referred to as the post-feverfew syndrome) (25).

Alteration of Coagulation Test Results and Vaginal Bleeding: In a 36-year-old woman with migraine after taking feverfew supplements (36).

Herb-Drug Interactions

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 (30). Clinical relevance is not known.

Anticoagulants/antiplatelets: The active constituent in feverfew inhibits platelet activity and may have additive effects (22) (23) (24) (31). Clinical relevance is not known.

Dosage (OneMSK Only)
References
  1. 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. doi: 10.1007/s00403-007-0818-x
  2. 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. doi: 10.1016/j.exppara.2007.08.015
  3. Mohsenzadeh F, Chehregani A, Amiri H. Chemical composition, antibacterial activity and cytotoxicity of essential oils of Tanacetum parthenium in different developmental stages. Pharm Biol. Sep 2011;49(9):920-926. doi: 10.3109/13880209.2011.556650
  4. Mathema VB, Koh YS, Thakuri BC, et al. Parthenolide, a sesquiterpene lactone, expresses multiple anti-cancer and anti-inflammatory activities. Inflammation. Apr 2012;35(2):560-565. doi: 10.1007/s10753-011-9346-0
  5. Wu C, Chen F, Wang X, et al. Identification of antioxidant phenolic compounds in feverfew (Tanacetum parthenium) by HPLC-ESI-MS/MS and NMR. Phytochem Anal. Sep-Oct 2007;18(5):401-410. doi: 10.1002/pca.995
  6. Diener HC, 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. Nov 2005;25(11):1031-1041. doi: 10.1111/j.1468-2982.2005.00950.x
  7. Cady RK, Goldstein J, Nett R, et al. A double-blind placebo-controlled pilot study of sublingual feverfew and ginger (LipiGesic M) in the treatment of migraine. Headache. Jul-Aug 2011;51(7):1078-1086. doi: 10.1111/j.1526-4610.2011.01910.x
  8. Ferro EC, Biagini AP, da Silva IE, et al. The combined effect of acupuncture and Tanacetum parthenium on quality of life in women with headache: randomised study. Acupunct Med. Dec 2012;30(4):252-257. doi: 10.1136/acupmed-2012-010195
  9. Pattrick M, Heptinstall S, Doherty M. Feverfew in rheumatoid arthritis: a double blind, placebo controlled study. Ann Rheum Dis. Jul 1989;48(7):547-549.
  10. Kim SL, Lee ST, Trang KT, et al. Parthenolide exerts inhibitory effects on angiogenesis through the downregulation of VEGF/VEGFRs in colorectal cancer. Int J Mol Med. May 2014;33(5):1261-1267. doi: 10.3892/ijmm.2014.1669
  11. Al-Fatlawi AA, Al-Fatlawi AA, Irshad M, et al. Effect of parthenolide on growth and apoptosis regulatory genes of human cancer cell lines. Pharm Biol. Jan 2015;53(1):104-109. doi: 10.3109/13880209.2014.911919
  12. Lu C, Wang W, Jia Y, et al. Inhibition of AMPK/autophagy potentiates parthenolide-induced apoptosis in human breast cancer cells. J Cell Biochem. Aug 2014;115(8):1458-1466. doi: 10.1002/jcb.24808
  13. Yip-Schneider MT, Nakshatri H, Sweeney CJ, et al. 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. doi: 10.1158/1535-7163.MCT-04-0215
  14. 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. doi: 10.1016/j.canlet.2004.03.033
  15. Parada-Turska J, Paduch R, Majdan M, et al. 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.
  16. Lesiak K, Koprowska K, Zalesna I, et al. 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. doi: 10.1097/CMR.0b013e328333bbe4
  17. Carlisi D, 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. Jun 2011;226(6):1632-1641. doi: 10.1002/jcp.22494
  18. 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. doi: 10.1023/B:DRUG.0000026256.38560.be
  19. Guzman ML, Rossi RM, Neelakantan S, et al. An orally bioavailable parthenolide analog selectively eradicates acute myelogenous leukemia stem and progenitor cells. Blood. Dec 15 2007;110(13):4427-4435. doi: 10.1182/blood-2007-05-090621
  20. Pareek A, Suthar M, Rathore GS, et al. Feverfew (Tanacetum parthenium L.): A systematic review. Pharmacogn Rev. Jan 2011;5(9):103-110. doi: 10.4103/0973-7847.79105
  21. Reuter U, Chiarugi A, Bolay H, et al. Nuclear factor-kappaB as a molecular target for migraine therapy. Ann Neurol. Apr 2002;51(4):507-516.
  22. Sahler J, Bernard JJ, Spinelli SL, et al. The feverfew plant-derived compound, parthenolide enhances platelet production and attenuates platelet activation through NF-kappaB inhibition. Thromb Res. May 2011;127(5):426-434. doi: 10.1016/j.thromres.2010.12.013
  23. Groenewegen WA, Heptinstall S. 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. Aug 1990;42(8):553-557.
  24. Heptinstall S, White A, Williamson L, et al. Extracts of feverfew inhibit granule secretion in blood platelets and polymorphonuclear leucocytes. Lancet. May 11 1985;1(8437):1071-1074.
  25. Johnson ES, Kadam NP, Hylands DM, et al. Efficacy of feverfew as prophylactic treatment of migraine. Br Med J (Clin Res Ed). Aug 31 1985;291(6495):569-573.
  26. Williams CA, Hoult JR, Harborne JB, et al. A biologically active lipophilic flavonol from Tanacetum parthenium. Phytochemistry. Jan 1995;38(1):267-270.
  27. Anderson KN, Bejcek BE. Parthenolide induces apoptosis in glioblastomas without affecting NF-kappaB. J Pharmacol Sci. Feb 2008;106(2):318-320.
  28. Paulsen E, Christensen LP, Andersen KE. Compositae dermatitis from airborne parthenolide. Br J Dermatol. Mar 2007;156(3):510-515. doi: 10.1111/j.1365-2133.2006.07674.x
  29. Killoran CE, Crawford GH, Pedvis-Leftick A. Two cases of compositae dermatitis exacerbated by moisturizer containing feverfew. Dermatitis. Dec 2007;18(4):225-229.
  30. 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):2273-2281. doi: 10.1002/rcm.1621
  31. Collins SC, Dufresne RG, Jr. Dietary supplements in the setting of mohs surgery. Dermatol Surg. Jun 2002;28(6):447-452.
  32. 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.
  33. Volta GD, Zavarise P, Perego L, Savi L, Pezzini A. Comparison of the Effect of Tanacethum Parthenium, 5-Hydroxy Tryptophan, and Magnesium (Aurastop) versus Magnesium Alone on Aura Phenomenon and Its Evolution. Pain Res Manag. 2019 Oct 9;2019:6320163.
  34. Hashimoto T, Yokozeki H. Occupational contact dermatitis caused by Eucalyptus species and Tanacetum parthenium. Contact Dermatitis. 2019 May;80(5):333-334.
  35. Lopresti AL, Smith SJ, Drummond PD. Herbal treatments for migraine: A systematic review of randomised-controlled studies. Phytother Res. 2020 Oct;34(10):2493-2517.
  36. Alenzi KA, Alharbi FH, Tawhari FM, Fradees GS. Alteration of Coagulation Test Results and Vaginal Bleeding Associated With the Use of Feverfew (Tanacetum parthenium). J Med Cases. 2021 Jan;12(1):9-12.
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