Feverfew - Tanacetum parthenium; a monograph

Updated: Jan 20

Herbal overview

Tanacetum parthenium has sometimes been confused with Matricaria chamomilla, since the two plants look very similar. Some traditional sources even suggest Feverfew has the same properties as Chamomile (Remington & Woods 1918, p.6); however this is not the case.


Traditionally Feverfew was mainly prescribed for female issues such as delivering afterbirth and strengthening the womb. Culpeper also prescribes it for shortness of breath and for expulsion of phlegm, as well as for melancholy and sadness in spirits. He does mention it as a remedy for headaches which have a cold causation. (1880, p.139) Few of these actions have been researched in recent times. Most notably the uterine tonic and emmenagogue actions are not discussed in modern literature other than with the caution for use in pregnancy. (Braun & Cohen 2015; Fisher 2009, p.54)


With a name which suggests it has febrile actions, no mention was found in modern literature or the available traditional literature of any such studies or claims, except one mention of the herb being an anti-pyretic in Carol Fisher’s book. (2009, p.54) However there was no justification given.


Nervous system - Migraine

One of the most researched modern uses for Feverfew is for migraines, both as a prophylactic, as well as a treatment. (Heinrich et al. 2012, p. 249).  According to Hwang et al. the first time this application was used was in 1972, when a Welsh woman cured her 50 year long suffering with a 10 month course of Feverfew, (cited in Saranitzky et al. 2009, p.92)


More than 50 studies have been performed on the efficacy of Feverfew in prophylactic treatment of migraines. A recent systemic review looked at 6 of these and found Feverfew to have an effect on some participants, but not enough to conclusively work as a treatment for the wider population. The conclusion is that Feverfew is promising as a migraine prophylactic but that more research needs to be done into the correct dose and delivery method. (Saranitzky et al. 2009, p.92-102)


Parthenolide is believed to be the key constituent in migraine management through several actions; anti-spasmodic, where it interferes with the contraction of blood vessel walls (Barnes et al. 2007, p.264); and by inhibiting the secretion of serotonin from platelet granules (Heinrich et al. 2012, p.249)


Not all extraction methods give the same result; De Weerdt suggests that Feverfew extracted with alcohol did not have any effect on migraines, suggesting that either alcohol is not a good solvent for parthenolide or that it extracts another constituent in greater amount which nullifies the effect of parthenolide (cited in Saranitzky et al. 2009, p.101)


Nervous system - Pain management

A study of Feverfew as an analgesic for other pain than migraines, found that parthenolide is an effective inflammatory, articular and neuropathic pain management agent. It also found that parthenolide is not the only constituent in Feverfew with analgesic effects. Two extracts were compared in the study, the flower and the leaf extracts. The flower extract was more effective than the leaf extract. (Mannelli et al. 2015, p. 754-757)


Both Galeotti and Nugroho found in more recent studies that there are several chemical compounds in the flower which are not found in the leaf, which probably explains the higher effect of the flower extract. (cited in Mannelli et al. 2015, p,757)


Musculoskeletal - arthritis

The key constituent parthenolide appears to be the most researched component of Feverfew (Bone & Mills 2013, p.567). It is also the one which provides the anti-inflammatory effects, which interact with arthritis. It might do this through controlling the production of lymphocytes and monocytes, the number of which is found to be high in the synovium of arthritic patients, and through inhibiting granular secretion in blood platelets and neutrophils. (Barnes et al. 2007, p.264)


A study from 2013 found a statistically significant improvement of pain for arthritis sufferers when taking Feverfew regularly over 4 weeks. It also found that joint-stiffness and functionality improved. (Rosen et al. p.31, 36)


Blood and Lymph

Feverfew has a number of interactions with platelets. It has been found that parthenolide stimulates platelet production, and as such is a potential new treatment for thrombocytopenic patients. The effect disappears quickly though, and much research needs to be done into delivery systems for best therapeutic effect. Interestingly parthenolide also inhibits platelet activation, which means that the platelets are unable to aggregate. (Sahler et al. 2011, p.427-434)


Feverfew could work as an anti-allergic through mast cell stabilisation. A study shows that parthenolide has significant effects on mediators (Miyata et al. 2008, p.879). However this study was done in vivo on rats and no studies with human subjects have been found.


Feverfew has been found in several studies to be anti-cancer; in fact parthenolide was patented in 2005 for cancer inhibition. It’s found to work well against leukaemia cells, but studies have had restricted results due to the substance being lipophilic and therefore having limited bioavailability. However, the studies have found parthenolide to be a potent epigenetic drug, which can have an effect on inhibiting cancer stem cells, and therefore stop metastasis or relapse. (Ghantous et al. 2013, p.894-903)

Furthermore, several of the constituents in


Feverfew have been found to be anti-microbial; parthenolide which inhibit growth of gram-positive bacteria as well as fungus and yeasts. Eudesmanolides has been found to act against E. coli, Salmonella as well as Staph. aureus. Additionally the essential oil from Feverfew has also been found to show activity against 27 different microorganisms.  (Bone & Mills 2013, p.570-571)


Digestive System

Traditionally Feverfew was applied topically to relieve severe pain or swelling of the bowels (Felter & Lloyd 1898, p.na; Culpeper 1880, p.na), and was praised for its carminative effect. Recent studies have shown that Feverfew has antispasmodic properties (Braun & Cohen 2015, p.317). Fisher suggests that the herbs bitter taste makes it useful for indigestion; making it a good stomachic (2009, p. 54).


Feverfew was also used traditionally as an anthelmintic (WARD 1936, p.45). A recent Brazilian study showed that the herb can be four times as effective when treating protozoa as the commonly used pharmaceutical benznidazole. This is especially interesting due to the severe side effects of the common drug. (Izumi et al. 2008, p. 329)


Liver

According to Braun and Cohen Feverfew has been found to be hepatoprotective through its anti-fibrotic activity and apoptotic effect (2015, p.318). No more evidence was found in literature regarding the hepatoprotective claims.  On a separate note however, the apoptotic effect has also been found to be effective in treating colon cancer (Kim et al. 2015, p.2141).


Female reproductive system

Several historical texts names Feverfew as a uterine tonic and stimulant which can assist in child birth or promote the menses (Culpeper 1880, p.139 ; Fox 1924, p.40; WARD 1936, p.45). As previously discussed; none of the modern text books mention these actions except to caution for use in pregnancy.


Integumentary

Interestingly a couple of studies have found Feverfew to be topically anti-inflammatory with the parthenolide removed - parthenolide depleted Feverfew or “PD”. Parthenolide can be hypo-allergenic on the skin, and with it removed, the herb was found to be a useful agent in skin creams. PD is claimed to protect skin from UV irradiation and other environmental aggressors, through preventing oxidative damage. One of the studies also found that PD can induce DNA repair in the skin.(Martin et al. 2007, p.78; Rodriguez et al. 2013, p.310) However the Martin et al. study was funded by Johnson & Johnson, so the results are dubious.


Safety data

Side effects

Feverfew can cause dermatitis as well as inflammation and ulceration of the mouth, however the effects are mild and did not result in patients discontinuing treatment (Pareek et al. 2011, p.7 ). The irritation is probably caused by the allergenic sesquiterpene lactones. (Heinrich et al. 2012, p. 249).


Prophylactic migraine prevention users who stop taking the herb have reported a “post Feverfew syndrome” with symptoms such as nervousness, insomnia, stiffness and pain in joints, as well as tiredness during a period post use. (Barnes et al. 2007, p.265)


During one study, a 63year old participant with multiple drug allergies as well as an autoimmune disease background, experienced facial oedema as well as non-specific pruritus, however both symptoms disappeared as soon as she discontinued use (Rosen et. al 2013, p.33), no other such symptoms have been found in literature.


Contraindications

Feverfew was historically used to expel the after birth, as an emmenagogue (Fisher 2009, p.55) and also known as an abortifacient (Pareek et al. 2011, p.8). Current literature warn against use during pregnancy (Braun & Cohen 2015, p. 321; Fisher 2009, p.55), at least during the first trimester and to keep dosage to a minimum throughout pregnancy (Bone & Mills 2013, p.574).


A recent study found that Feverfew can have a adverse effect in pregnancy on rats when dosed 59 times the acceptable human dose (Yao et al. 2006, p. 692). This study found that parthenolide can cross the placenta and have an adverse effect on the fetus. However, this appears to be the only study on parthenolide’s effect on pregnancy.

Furthermore, the herb is not recommended in lactating mothers or  in children (Pareek et al. 2011, p.9).


Drug interactions

The anti-platelet action of the herb, which could extend bleeding time, could interact with anticoagulants and alter the effects of these medications (Pareek et al.2011, p.7). Patients on anticoagulants who take Feverfew should be observed (Braun & Cohen 2015, p.321)


Prescriptive forms


Avoid alcohol based extracts in migraine management; since alcohol based feverfew extracts have been found to have a less to none effect for this application. (Saranitzky et al. 2009, p.101)

The migraine prophylaxis will need to be taken for 4-6 months before the effect can be seen. (Pareek et al. 2011, p.103)


No dosage recommendation for cancer treatment was found in reviewed literature.


No recommendation for taking the herb with or before meals was found in the reviewed literature.


References

Barnes, J, Anderson, L & Phillipson, D 2007, Herbal Medicine, 3rd edn, Pharmaceutical Press, London.


Bone, K & Mills, S 2013, Principles and practice of phytotherapy : modern herbal medicine, Churchill Livingstone.


Braun, L & Cohen, M 2015, Herbs & natural supplements : an evidence-based guide. volume 2, 4th edn, Elsevier Health Sciences APAC, Saint Louis.


Culpepper, N 1880, Complete Herbal, W. Foulsham and Co. Ltd, London.

Felter, HW & Lloyd, JU 1898, King’s American Dispensatory, 18th edn, Ohio Valley Co, Cincinnatti, viewed 13 September 2016, <http://www.henriettes-herb.com/eclectic/kings>.


Fisher, C 2009, Materica Medica of Western Herbs, Carole Fisher, Nelson, NZ.


Fox, W 1924, The Working Man’s Model Family Botanic Guide, 23rd edn, William


Fox and Sons, Sheffield.

Ghantous, A, Sinjab, A, Herceg, Z & Darwiche, N 2013, ‘Parthenolide: from plant shoots to cancer roots’, Drug Discovery Today, vol. 18, no. 17, pp. 894–905.


Heinrich, M, Kinghorn, AD, Phillipson, JD, Maizels, D & Gibbons, S 2012, Fundamentals of pharmacognosy and phytotherapy, 2nd edn, Elsevier, Edinburgh.


Izumi, E, Morello, LG, Ueda-Nakamura, T, Yamada-Ogatta, SF, Filho, BPD, Cortez, DAG, Ferreira, ICP, Morgado-Díaz, JA & Nakamura, CV 2008, ‘Trypanosoma cruzi: Antiprotozoal activity of parthenolide obtained from Tanacetum parthenium (L.) Schultz Bip. (Asteraceae, Compositae) against epimastigote and amastigote forms’, Experimental Parasitology, vol. 118, no. 3, pp. 324–330.


Kim, S, Liu, Y, Seo, S, Kim, S, Kim, I, Lee, S, Lee, S, Kim, D & Kim, S 2015, ‘Parthenolide induces apoptosis in colitis-associated colon cancer, inhibiting NF-κB signaling’, Oncology Letters, viewed 19 September 2016, <http://www.spandidos-publications.com/10.3892/ol.2015.3017>.


Mannelli, LD-C, Tenci, B, Zanardelli, M, Maidecchi, A, Lugli, A, Mattoli, L & Ghelardini, C 2015, ‘Widespread pain reliever profile of a flower extract of Tanacetum parthenium’, Phytomedicine, vol. 22, no. 7, pp. 752–758.


Martin, K, Sur, R, Liebel, F, Tierney, N, Lyte, P, Garay, M, Oddos, T, Anthonavage, M, Shapiro, S & Southall, M 2007, ‘Parthenolide-depleted Feverfew (Tanacetum parthenium) protects skin from UV irradiation and external aggression’, Johnson & Johnson Skin Research Center.


Mills, S & Bones, K 2000, Principles and Practice of Phytotherapy, Harcourt Publishers Limited, London.


Minyata, N, Gon, Y, Nunomura, S, Endo, D, Yamashita, K, Matsumoto, K, Hashimoto, S & Ra, C 2008, ‘Inhibitory effects of parthenolide on antigen-induced microtubule formation and degranulation in mast cells’, International Immunopharmacology, vol. 8, no. 6, pp. 874–880.


Pareek, A, Suthar, M, Rathore, G & Bansal, V 2011, ‘Feverfew (Tanacetum parthenium L.): A systematic review’, Pharmacognosy Reviews, p. p.103, viewed 1 January 2016, <http://www.phcogrev.com/>.


Pengelly, A 2004, The Constituents of Medicinal Plants : An Introduction to the Chemistry and Therapeutics of Herbal Medicine, Allen & Unwin, Crows Nest, NSW, viewed 1 January 2016, <http://web.b.ebscohost.com>.


Remington, JP & Woods, HC (eds) 1918, The Dispensatory of the United States of America, 20th edn, Lippincott, Philadelphia, viewed 20 September 2016, <http://www.henriettes-herb.com/eclectic/usdisp>.


Rodriguez, KJ, Wong, H-K, Oddos, T, Southall, M, Frei, B & Kaur, S 2013, ‘A purified Feverfew extract protects from oxidative damage by inducing DNA repair in skin cells via a PI3-kinase-dependent Nrf2/ARE pathway’, Journal of Dermatological Science, vol. 72, no. 3, pp. 304–310.


Rosen, P, Liakeas, G, Sadigim, E & Bied, A 2013, ‘A Pilot Study Assessing the Short-term Use of Tanacetum parthenium for Treatment of Osteoarthritis.’, Integrative Medicine: A Clinician’s Journal, vol. 12, no. 3, pp. 31–36.


Sahler, J, Bernard, JJ, Spinelli, SL, Blumberg, N & Phipps, RP 2011, ‘The Feverfew plant-derived compound, parthenolide enhances platelet production and attenuates platelet activation through NF-κB inhibition’, Thrombosis Research, vol. 127, no. 5, pp. 426–434.


Saranitzky, E, White, CM, Baker, EL, Baker, WL & Coleman, CI 2009, ‘Feverfew for migraine prophylaxis: a systematic review.’, Journal of dietary supplements, vol. 6, no. 2, pp. 91–103, viewed 14 September 2016, <http://www.ncbi.nlm.nih.gov/pubmed/22435410>.


The Council of Heads of Australasian Herbaria 2011, APC Format - Tanacetum parthenium, viewed 13 September 2016, <https://biodiversity.org.au/nsl/services/apc-format/display/116715>.


WARD, H 1936, HERBAL MANUAL - The Medicinal, Toilet, Culinary and other Uses of 130 of the Commonly Used Herbs, L. N. Fowler & Co. Ltd. (ed.), London.


Yao, M, Ritchie, HE & Brown-Woodman, PD 2006, ‘A Reproductive screening test of feverfew: Is a full reproductive study warranted?’, Reproductive Toxicology, vol. 22, no. 4, pp. 688–693.

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