Feverfew

Feverfew Summary

Feverfew is quite likely the best herbal treatment for chronic migraine headaches. This condition has many different mechanisms, and is not well understood by medicine even today. There are several major theories as to the pathophysiology of migraine headaches, and feverfew has phytochemicals that address them all.

Despite its name, feverfew is not useful for treating fevers, but has antiallergenic, anti-inflammatory, vasodilating, and antisecretory activities instead.

Indications

• Migraines
• Tension headaches
• Dizziness
• Tinnitus
• Fever
• Nervous debility
• Painful periods
• Sluggish menstrual flow
• Arthritis
• Parasites
• Coughs
• Colds
• Atonic dyspepsia

Contraindications

• Warfarin
• Mouth ulceration

How Is Feverfew Used?

Feverfew’s main use is for migraine headaches, where it excels, especially with recurrent migraines that are characterized by finding relief from applying heat. Feverfew is also useful for female reproductive issues including painful menstruation and sluggish menstrual flow.

Traditional Uses

Western Herbal Medicine

Traditionally feverfew was used as a decoction with sugar or honey to treat coughs, wheezing, and difficulty breathing ^{5Reference 5A Modern Herbal · 1931FeverfewView study →}. It was used as a warm infusion to purge choler, treat colds/flus, fever, cleanse the kidneys, stimulate menstruation, and expel parasitic worms ^{8Reference 8Bone K · 2013Principles and Practice of Phytotherapy}. It was decocted to treat wheezing, coughs, and difficulty breathing. A cold infusion was used as a tonic, and for opium overdoses.

Topically, the herb was used by bruising and heating with a little oil, and applied for conditions such as wind and colic. The tincture was also used topically to treat pain and swelling from insect and animal bites to offer fast relief ^{5Reference 5A Modern Herbal · 1931FeverfewView study →}. As a poultice it was used to reduce pain and inflammation of the bowel, and for wind or colic conditions ^{8Reference 8Bone K · 2013Principles and Practice of Phytotherapy}.

It was described by Dioscorides as useful for “all hot inflammations” ^{1Reference 1Pareek et al. · 2011Systematic reviewFeverfew (Tanacetum parthenium L.): A systematic reviewView study →},

There was very little reference to feverfews actions on migraine headaches ^{8Reference 8Bone K · 2013Principles and Practice of Phytotherapy}, despite this being one of the main uses of this plant today.

South American Traditional Medicine

In South America, the Kallaway Indians of the Andes mountains used feverfew for treating conditions such as colic, kidney pain, morning sickness, and stomach aches ^{1Reference 1Pareek et al. · 2011Systematic reviewFeverfew (Tanacetum parthenium L.): A systematic reviewView study →}. In other areas of South and Central America feverfew was used to support digestion, as a cardiotonic, emmenagogue, antispasmodic, menstrual tonic, treating earaches, and in the form of an enema for worms ^{2Reference 2Chavez M · 1999Feverfew}.

Botanical Information

Feverfew is a member of the Asteraceae family of plants, which is the second largest flowering family only to orchids. Feverfew is further separated into the Anthemideae tribe which is also home to such other medicinal species including the sages and yarrow.

Feverfew is an aromatic perennial herb, growing to a height of around 70 cm. The leaves are light green, and ovate with pinnatifid lobed or toothed leaflets ^{1,8Reference 1Pareek et al. · 2011Systematic reviewFeverfew (Tanacetum parthenium L.): A systematic reviewView study →Reference 8Bone K · 2013Principles and Practice of Phytotherapy}.

The flowers resemble that of chamomiles.

Habitat, Ecology & Distribution

Feverfew is native to the Balkan Peninsula, and can now also be found in Australia, Europe, China, Japan, and North Africa, United states, and Canada. It’s usually found growing along roadsides, in fields, and waste areas. ^{1Reference 1Pareek et al. · 2011Systematic reviewFeverfew (Tanacetum parthenium L.): A systematic reviewView study →}.

Harvesting, Collection & Preparation

The parthenolide content from feverfew varies greatly depending on the growing conditions. This is important because this is suggested to be one of the main constituents responsible for feverfews ability to reduce the severity of and/or prevent migraine headaches. This is why it’s suggested that a standardized extract of feverfew should be used, containing at least a 0.2% parthenolide content (per 125mg dried feverfew leaf equivalent) ^{6Reference 6Hoffmann · 2003Medical herbalism: The science and practice of herbal medicine}.

The leaves (and sometimes stems) are collected during, or after flowering ^{8Reference 8Bone K · 2013Principles and Practice of Phytotherapy}.

Pharmacology & Medical Research

Anti-Allergenic

Some of the antisecretory, anti-allergenic, and antihistamine activity of feverfew acts on the mast cells by inhibiting the release of histamine. Parthenolide was found to inhibit rat peritoneal mast cell degranulation and release of histamine, as well as inhibited passive cutaneous anaphylaxis in mice. These effects were noted to be dose dependant (meaning that a higher dose will increase or improve this activity). ^{8Reference 8Bone K · 2013Principles and Practice of Phytotherapy}. The mechanism of action has been suggested to involve the mediation of calcium entry into mast cells ^{16Reference 16Hayes NA · 1987AnimalThe activity of compounds extracted from feverfew on histamine release from rat mast cells}.

Anti-Inflammatory

The anti-inflammatory actions of feverfew are mainly via an inhibition of NF-kB activation, and inhibition of prostaglandin biosynthesis ^{8Reference 8Bone K · 2013Principles and Practice of Phytotherapy}. Parthenolide specifically binds to and inhibits the IkB kinase complex, which plays an important role in the pro-inflammatory cytokine mediated signalling ^{15Reference 15Kwok BH et al. · 2001The anti-inflammatory natural product parthenolide from the medicinal herb feverfew directly binds to and inhibits IkappaB kinase}.

Migraine Headaches

Feverfew is considered the best herbal treatment for migraines ^{6Reference 6Hoffmann · 2003Medical herbalism: The science and practice of herbal medicine}. It’s best used as a long term treatment, rather than for immediate relief. In the 1980’s, due to widespread media coverage for the use of feverfew as a “cure” for migraines, a few doctors took it upon themselves to observe the effect of this herb on their patients and submitted their results to an online journal. In one double-blind, placebo controlled clinical trial investigating these effects, feverfew was found to produce a significant reduction in migraine headache frequency compared to the control group. ^{6,7Reference 6Hoffmann · 2003Medical herbalism: The science and practice of herbal medicineReference 7Johnson ES et al. · 1985Efficacy of feverfew as prophylactic treatment of migraine}.

The mechanism of action for this is reported to be through inhibiting the secretion of granular contents from blood platelets and neutrophils such as prostaglandins, and histamine. The constituents suggested to be responsible are mainly the sesquiterpene lactones; 3-beta-hydroxy-parthenolide, secotanapartholide A, canin, and artecanin. ^{6Reference 6Hoffmann · 2003Medical herbalism: The science and practice of herbal medicine}.

Although the above theories stand to reason as to how feverfew acts on migraine headaches, much of the mechanisms of action for this condition remains elusive to science. Therefore it’s hard to pinpoint how chemicals such as those contained wihin feverfew truly work within the body for this condition. Currently, the suggestions for feverfews possible mechanism of action(s) on treating migraine headaches includes:

1. Inhibiting serotonin release from platelet triggers (which is thought to lead to a complex chain reaction leading to migraine attacks) ^{1,8Reference 1Pareek et al. · 2011Systematic reviewFeverfew (Tanacetum parthenium L.): A systematic reviewView study →Reference 8Bone K · 2013Principles and Practice of Phytotherapy}.
2. Anti-inflammatory activity in migraines due mainly to the partenolide content. This differs from other anti-inflammatory drugs because of how specific parthenolide is on how it inhibits NF-kB through a variety of biochemical pathways ^{8Reference 8Bone K · 2013Principles and Practice of Phytotherapy}.
3. Decrease of vascular smooth muscle spasm ^{1,17Reference 1Pareek et al. · 2011Systematic reviewFeverfew (Tanacetum parthenium L.): A systematic reviewView study →Reference 17Barsby RW et al. · 1992Feverfew extracts and parthenolide irreversibly inhibit vascular responses of the rabbit aorta}.
4. Blockage of platelet granule secretion ^{1,18Reference 1Pareek et al. · 2011Systematic reviewFeverfew (Tanacetum parthenium L.): A systematic reviewView study →Reference 18Heptinstall S et al. · 1985Extracts of feverfew inhibit granule secretion in blood platelets and polymorphonuclear leucocytes}.

Phytochemistry

Feverfew’s therapeutic identity rests on its sesquiterpene lactones, above all the germacranolide parthenolide — the compound to which products are standardised and which accounts for the bulk of the herb’s anti-inflammatory and anti-migraine activity. Parthenolide can make up as much as ~85% of the total sesquiterpene lactone content but is highly variable; standardised extracts target a minimum of 0.2% ^{3,8Reference 3Setty AR · 2005Herbal medications commonly used in the practice of rheumatology: Mechanisms of action, efficacy, and side effectsReference 8Bone K · 2013Principles and Practice of Phytotherapy}. It is accompanied by a large family of related lactones including costunolide, canin, artecanin, and secotanapartholide A.

The aerial parts also yield a camphor-rich volatile oil, a suite of methylated flavonoids (tanetin, santin, apigenin, luteolin) with their own anti-inflammatory activity, decaffeoylquinic acids, and polyacetylenes ^{9,10,11,12,13,14Reference 9Akpulat H et al. · 2005Composition of the essential oils of Tanacetum argyrophyllum (CReference 10Williams CA et al. · 1999Variations in lipophilic and polar flavonoids in the genus TanacetumReference 11Williams CA et al. · 1999The flavonoids of Tanacetum parthenium and T. vulgare and their anti-inflammatory propertiesReference 12Williams CA et al. · 1995A biologically active lipophilic flavonol from Tanacetum partheniumReference 13Long C et al. · 2003Bioactive flavonoids ofTanacetum parthenium revisitedReference 14Hall I et al. · 1979Anti-inflammatory activity sesquiterpene lactones and related compounds}.

Constituent Summary

Parthenolide is given as percent of dried herb; volatile-oil components as percent of the oil (from one Turkish chemotype, ref ^{9Reference 9Akpulat H et al. · 2005Composition of the essential oils of Tanacetum argyrophyllum (C}) — both vary greatly with genetics, harvest time and growing conditions. Entries marked No Data are documented qualitatively only ^{3,8,9Reference 3Setty AR · 2005Herbal medications commonly used in the practice of rheumatology: Mechanisms of action, efficacy, and side effectsReference 8Bone K · 2013Principles and Practice of PhytotherapyReference 9Akpulat H et al. · 2005Composition of the essential oils of Tanacetum argyrophyllum (C}.

Sesquiterpene lactones

Grouped by class · 7 compoundsExpand all|Collapse all

GroupCompoundAmount

Sesquiterpene Lactone7 compounds1 with data

Sesquiterpene LactoneParthenolide~0.2–1.8% (dried herb); up to ~85% of total SLs

Sesquiterpene LactoneCostunolideNo data

Sesquiterpene LactoneCaninNo data

Sesquiterpene LactoneArtecaninNo data

Sesquiterpene LactoneSecotanapartholide ANo data

Sesquiterpene LactoneSantamarinNo data

Sesquiterpene LactoneReynosinNo data

Volatile oil

Grouped by class · 5 compoundsExpand all|Collapse all

GroupCompoundAmount

Monoterpene5 compounds4 with data

MonoterpeneCamphor~56.9% of oil

MonoterpeneCamphene~12.7% of oil

Monoterpenep-Cymene~5.2% of oil

MonoterpeneBornyl acetate~4.6% of oil

Monoterpene1,8-CineoleNo data

Flavonoids

Grouped by class · 5 compoundsExpand all|Collapse all

GroupCompoundAmount

Flavonoid5 compoundsno data

FlavonoidApigeninNo data

FlavonoidLuteolinNo data

FlavonoidTanetinNo data

FlavonoidSantinNo data

FlavonoidJaceidinNo data

The parthenolide content of feverfew is associated with much of its therapeutic actions, especially in migraine treatment. This chemical however will vary greatly in different plant samples. It’s suggested that it can be improved by harvesting the plant in the afternoon, and after a single water stress event. It’s also noted that varieties with a light green/yellow leaf color yield higher concentrations of parthenolide. ^{8Reference 8Bone K · 2013Principles and Practice of Phytotherapy}.

Clinical Applications

Feverfew is a reliable treatment for migraine headaches. The effects are not immediate, and require gradual long term use to be effective. For this reason it’s common to use feverfew alongside pharmaceutical painkillers for symptomatic relief with migraines. After gradual use of feverfew the episodes become shorter, less frequent, and less severe.

Feverfew is also useful for its antiallergenic activities due to its ability to inhibit histamine. Again, this is a long term treatment and will not produce effects after a single dose. For this reason immediate symptomatic relief is often combined with pharmaceutical antihistamines in the early stages of treatment.

Cautions & Safety

Feverfew has been known to cause mouth ulceration.

Do not exceed 1.5 ml/day of 1:5 tincture while pregnant ^{4Reference 4Bone · 2003A clinical guide to blending liquid herbs: Herbal formulations for the individual patient}

May interact with aspirin or other anticoagulant drugs due to a similar mechanism of action.

Synergy

May be synergistic with Gingko biloba for migraine headache.

References

1. Pareek, A., Suthar, M., Rathore, G., & Bansal, V. (2011). Feverfew (Tanacetum parthenium L.): A systematic review. Pharmacognosy Reviews, 5(9), 103. doi:10.4103/0973-7847.79105
2. Chavez M, Chavez P. (1999). Feverfew. Hosp Pharm. 34:436–61.
3. Setty AR, Sigal AH. (2005). Herbal medications commonly used in the practice of rheumatology: Mechanisms of action, efficacy, and side effects. Semin Arthritis Rheum. 34:773–84.
4. Bone, K. (2003). A clinical guide to blending liquid herbs: Herbal formulations for the individual patient. Edinburgh [u.a.: Churchill Livingstone. (Pg. 219-221)
5. A Modern Herbal. (1931). Feverfew. Retrieved from http://www.botanical.com/botanical/mgmh/f/feverf10.html
6. Hoffmann, D. (2003). Medical herbalism: The science and practice of herbal medicine. Rochester, VT: Healing Arts Press. (Pg. 5587)
7. Johnson ES, Kadam NP, Hylands DM. (1985). Efficacy of feverfew as prophylactic treatment of migraine. British medical journal (Clinical research Ed.) 291:569-573
8. Bone K, Mills S. (2013). Principles and Practice of Phytotherapy. Elsevier health. China. (Pg. 566-575)
9. Akpulat H, Tepe B, Sokmen A, Daferera D, Polissiou M. (2005). Composition of the essential oils of Tanacetum argyrophyllum (C. Koch) Tvzel. var. argyrophyllum and Tanacetum parthenium (L.) Schultz Bip. (Asteraceae) from Turkey. Biochem Syst Ecol. 33:511–6.
10. Williams CA, Harborne JB, Eagles J. (1999). Variations in lipophilic and polar flavonoids in the genus Tanacetum. Phytochemistry. 52:1301–6.
11. Williams CA, Harborne JB, Geiger H, Hoult JR. (1999). The flavonoids of Tanacetum parthenium and T. vulgare and their anti-inflammatory properties. Phytochemistry. 51:417–23.
12. Williams CA, Hoult JR, Harborne JB, Greenham J, Eagles J. (1995). A biologically active lipophilic flavonol from Tanacetum parthenium. Phytochemistry. 38:267–70.
13. Long C, Sauleau P, David B. (2003). Bioactive flavonoids ofTanacetum parthenium revisited. Phytochemistry. 64:567–9.
14. Hall I, Lee K, Starnes C, Sumida Y, Wu R, Waddell T. (1979). Anti-inflammatory activity sesquiterpene lactones and related compounds. J Pharm Sci. 68:537–42.
15. Kwok BH, Koh B, Ndubuisi MI, Elofsson M, Crews CM. (2001). The anti-inflammatory natural product parthenolide from the medicinal herb feverfew directly binds to and inhibits IkappaB kinase. Chem Biol. 8:759–66.
16. Hayes NA, Foreman JC. (1987). The activity of compounds extracted from feverfew on histamine release from rat mast cells. J Pharm Pharmacol. 39:466–70.
17. Barsby RW, Salan U, Knight DW, Hoult JR. (1992). Feverfew extracts and parthenolide irreversibly inhibit vascular responses of the rabbit aorta. J Pharm Pharmacol. 44:737–40.
18. Heptinstall S, White A, Williamson L, Mitchell JR. (1985). Extracts of feverfew inhibit granule secretion in blood platelets and polymorphonuclear leucocytes. Lancet. 1:1071–4.