Feverfew

The first-century Greek physician Dioscorides prescribed feverfew for “all hot inflammations” and used it to reduce fever ^{8Reference 8Pareek et al. · 2011Systematic reviewFeverfew (Tanacetum parthenium L.): A systematic reviewView study →}.

A decoction with sugar or honey was taken for coughs, wheezing and difficult breathing ^{23Reference 23A Modern Herbal · 1931Feverfew. http://www.botanical.com/botanical/mgmh/f/feverf10.htmlView study →}. A warm infusion was used to “purge choler”, to treat colds, flu and fever, to cleanse the kidneys, to bring on menstruation and to expel worms ^{24Reference 24Bone K · 2013Principles and Practice of Phytotherapy}.

A cold infusion served as a tonic, and the herb was given for overindulgence in opium ^{8,24Reference 8Pareek et al. · 2011Systematic reviewFeverfew (Tanacetum parthenium L.): A systematic reviewView study →Reference 24Bone K · 2013Principles and Practice of Phytotherapy}.

Applied externally, the herb was bruised and warmed with a little wine and oil for wind and colic. A tincture was used to relieve the pain and swelling of insect bites ^{23Reference 23A Modern Herbal · 1931Feverfew. http://www.botanical.com/botanical/mgmh/f/feverf10.htmlView study →}.

The fresh or dried leaves were also eaten directly, two or three a day, often sweetened because of their bitterness ^{8Reference 8Pareek et al. · 2011Systematic reviewFeverfew (Tanacetum parthenium L.): A systematic reviewView study →}.

The older herbals say little about migraine, the use for which feverfew is now best known ^{24Reference 24Bone K · 2013Principles and Practice of Phytotherapy}. The first modern public account of feverfew as a migraine preventive appeared in a British health magazine in 1978 ^{8Reference 8Pareek et al. · 2011Systematic reviewFeverfew (Tanacetum parthenium L.): A systematic reviewView study →}.

Kallawaya healers of the Andes use feverfew for colic, kidney pain, morning sickness and stomach ache ^{8Reference 8Pareek et al. · 2011Systematic reviewFeverfew (Tanacetum parthenium L.): A systematic reviewView study →}.

In Costa Rica a decoction is taken to aid digestion, as a heart tonic and to bring on menstruation, and as an enema for worms. In Mexico it is used as an antispasmodic and a menstrual tonic, and in Venezuela for earache ^{8,21Reference 8Pareek et al. · 2011Systematic reviewFeverfew (Tanacetum parthenium L.): A systematic reviewView study →Reference 21Chavez M · 1999Feverfew}.

Cochrane’s 2015 review found three small positive trials (17–60 participants) and two rigorous trials (50 and 147 participants) that found no significant difference from placebo ^{1Reference 1Wider et al. · 2015Systematic reviewFeverfew for preventing migraine — systematic reviewView study →}.

Two of the positive trials enrolled people who had already had good results with feverfew ^{6Reference 6De Weerdt et al. · 1996RCTHerbal medicines in migraine prevention — randomized double-blind placebo-controlled crossover trial of a feverfew preparationView study →}. In the 1985 trial, 17 patients who were already eating the fresh leaves were given capsules. Those switched to placebo had more frequent and more severe headaches, while those kept on feverfew showed no change ^{5Reference 5Johnson et al. · 1985RCTEfficacy of feverfew as prophylactic treatment of migraine — randomised placebo-controlled trialView study →}.

In the 1988 crossover trial, 72 volunteers took one capsule of dried leaf a day or placebo for four months each, and 59 were analysed. Feverfew reduced the number and severity of attacks and the degree of vomiting, but not the length of attacks ^{4Reference 4Murphy et al. · 1988RCTRandomised double-blind placebo-controlled trial of feverfew in migraine preventionView study →}.

In a 1996 crossover trial in 50 people who had never used feverfew, an alcoholic extract containing 0.5 mg parthenolide a day had no effect on the number of attacks ^{6Reference 6De Weerdt et al. · 1996RCTHerbal medicines in migraine prevention — randomized double-blind placebo-controlled crossover trial of a feverfew preparationView study →}.

A 2002 dose-finding trial of a stable supercritical-CO₂ extract (MIG-99) in 147 patients found no overall effect. A benefit appeared only in a predefined subgroup of 49 patients with at least four attacks a month, and was largest at 6.25 mg three times daily ^{3Reference 3Pfaffenrath et al. · 2002RCTThe efficacy and safety of Tanacetum parthenium (feverfew) in migraine prophylaxis — a double-blind, multicentre, randomized placebo-controlled dose-response studyView study →}.

A 16-week trial then tested that dose in 170 patients. Attacks fell from about 4.8 a month by 1.9 on feverfew and by 1.3 on placebo, a difference of about 0.6 attacks a month, with no difference in the intensity or length of attacks ^{1,2Reference 1Wider et al. · 2015Systematic reviewFeverfew for preventing migraine — systematic reviewView study →Reference 2Diener et al. · 2005RCTEfficacy and safety of 6.25 mg t.i.d. feverfew CO2-extract (MIG-99) in migraine prevention — randomized, double-blind, placebo-controlled studyView study →}.

Cochrane concluded that this adds some positive evidence but that the evidence is low quality and needs confirming in larger trials ^{1Reference 1Wider et al. · 2015Systematic reviewFeverfew for preventing migraine — systematic reviewView study →}. A 2025 meta-analysis of nine trials with 899 participants found fewer and shorter attacks but no significant effect on pain severity, and judged the benefit modest ^{7Reference 7Nelaturi et al. · 2025Meta-analysisSystematic review and meta-analysis of Tanacetum parthenium: evaluating its efficacy in migraine relief — meta-analysisView study →}. A 2020 systematic review of single-herb migraine trials also found the feverfew results mixed ^{33Reference 33Lopresti AL et al. · 2020Systematic reviewHerbal treatments for migraine: A systematic review of randomised-controlled studies — systematic reviewView study →}.

In hypothalamic cells, a commercial feverfew water extract reduced dopamine release, which the authors put down to parthenolide binding the dopamine transporter. In the same study it damped inflammatory signals in mouse cortex exposed to a model of cortical spreading depression, the brain event behind migraine aura ^{34Reference 34Recinella L et al. · 2020In vitroAnti-Inflammatory and Neuromodulatory Effects Induced by Tanacetum parthenium Water Extract: Results from In Silico, In Vitro and Ex Vivo StudiesView study →}.

Gap: no trial has replicated the MIG-99 result at scale; the effect is small and extract-specific, and does not transfer to teas, whole-leaf powder or other extracts.

Parthenolide binds directly to cysteine-179 of IKKβ and inhibits it, which blocks NF-κB-driven inflammatory signalling. Its anti-inflammatory activity in vitro and in vivo depends on the α-methylene-γ-lactone group that it shares with other sesquiterpene lactones ^{9Reference 9Kwok et al. · 2001In vitroThe anti-inflammatory natural product parthenolide from the medicinal herb feverfew directly binds to and inhibits IκB kinase — in vitroView study →}.

Feverfew extracts also inhibit secretion from platelets and neutrophils. They block serotonin release and platelet aggregation, but not thromboxane synthesis ^{10Reference 10Heptinstall et al. · 1985In vitroExtracts of feverfew inhibit granule secretion in blood platelets and polymorphonuclear leucocytes — in vitroView study →}.

The lipophilic flavonoids of feverfew, methyl ethers of 6-hydroxykaempferol and quercetagetin such as tanetin, inhibit cyclo-oxygenase and 5-lipoxygenase in white cells ^{13Reference 13Williams et al. · 1999In vitroThe flavonoids of Tanacetum parthenium and T. vulgare and their anti-inflammatory properties — in vitroView study →}.

A commercial water extract, a preparation close to the traditional infusion, lowered prostaglandin E2 release and interleukin-1β expression and raised interleukin-10 and BDNF expression in isolated mouse cortex ^{34Reference 34Recinella L et al. · 2020In vitroAnti-Inflammatory and Neuromodulatory Effects Induced by Tanacetum parthenium Water Extract: Results from In Silico, In Vitro and Ex Vivo StudiesView study →}.

The one clinical test in an inflammatory disease was negative. In a double-blind trial, 70–86 mg of dried feverfew daily for six weeks gave no benefit on any clinical or laboratory measure in 41 women with rheumatoid arthritis ^{17Reference 17Pattrick et al. · 1989RCTFeverfew in rheumatoid arthritis: a double-blind, placebo-controlled study — randomised controlled trialView study →}.

Gap: rich in vitro and mechanistic data, but a negative human trial in the one inflammatory disease tested.

Parthenolide induced apoptosis in primary human acute myeloid leukaemia (AML) and blast-crisis CML cells while sparing normal blood cells. In colony assays and a NOD/SCID mouse xenograft model it preferentially targeted leukaemia stem and progenitor cells, and it was far more specific to leukaemia cells than the standard drug cytarabine ^{14Reference 14Guzman et al. · 2005In vitroThe sesquiterpene lactone parthenolide induces apoptosis of human acute myelogenous leukemia stem and progenitor cells — in vitro / animal modelView study →}.

Native parthenolide has poor pharmacological properties, so an analogue, dimethylamino-parthenolide (DMAPT), was developed. It has about 70% oral bioavailability, kills leukaemia stem cells through oxidative stress, NF-κB inhibition and p53 activation, and was active in mouse xenografts and in dogs with spontaneous leukaemia ^{15Reference 15Guzman et al. · 2007In vitroAn orally bioavailable parthenolide analog selectively eradicates acute myelogenous leukemia stem and progenitor cells — in vitro / animal modelView study →}.

Parthenolide has also reduced proliferation and invasion and induced apoptosis in colorectal cancer cell lines, through NF-κB ^{16Reference 16Gehren et al. · 2023In vitroParthenolide inhibits proliferation and invasion, promotes apoptosis, and reverts cell–cell adhesion loss through downregulation of the TNF-α-activated NF-κB pathway in colorectal cancer cells — in vitroView study →}.

Gap: entirely preclinical, and it is isolated parthenolide or a synthetic analogue that produces these effects, not feverfew tea, tincture or leaf; no clinical oncology use is supported.

A feverfew extract produced a dose-dependent inhibition of histamine release from rat mast cells stimulated with anti-IgE. It acted differently from cromoglycate and quercetin, and the authors described it as a new type of mast-cell inhibitor ^{12Reference 12Hayes et al. · 1987AnimalThe activity of compounds extracted from feverfew on histamine release from rat mast cells — animal modelView study →}.

Feverfew extracts also inhibit serotonin release and granule secretion from platelets and neutrophils. The effect on neutrophils was stronger than that of very high concentrations of NSAIDs ^{10Reference 10Heptinstall et al. · 1985In vitroExtracts of feverfew inhibit granule secretion in blood platelets and polymorphonuclear leucocytes — in vitroView study →}.

In human platelets, crude extract and isolated parthenolide had closely similar effects on serotonin secretion and aggregation, which suggests that parthenolide or related compounds carry the activity, possibly through the protein kinase C pathway ^{35Reference 35Groenewegen WA · 1990In vitroA comparison of the effects of an extract of feverfew and parthenolide, a component of feverfew, on human platelet activity in-vitro — in vitroView study →}.

Gap: animal and cell data only, with no human trials of feverfew for allergy, rhinitis or urticaria.

A purified, parthenolide-depleted feverfew extract activated the Nrf2/ARE antioxidant pathway in human skin cells through PI3-kinase, and reduced UV-induced DNA damage in vitro ^{20Reference 20Rodriguez et al. · 2013In vitroA purified feverfew extract protects from oxidative damage by inducing DNA repair in skin cells via a PI3-kinase-dependent Nrf2/ARE pathway — in vitroView study →}.

This is the basis of feverfew’s use in cosmetics. The ingredient is stripped of parthenolide, the compound behind both the migraine activity and the herb’s contact allergy.

Gap: one in vitro study of a modified extract, with no clinical skin outcomes.

In rodents, a hydroalcoholic feverfew extract (10–100 mg/kg) and isolated parthenolide (5 and 50 mg/kg) reduced stomach ulcers caused by ethanol and by the painkiller piroxicam, which was confirmed under the microscope. The extract also reduced acid secretion in the pylorus-ligation model ^{32Reference 32Ferraz CV et al. · 2026AnimalTanacetum parthenium and parthenolide increase defensive agents and promote antisecretory activity supporting their gastroprotective actions in rodentsView study →}.

The protection disappeared when nitric oxide, adrenergic receptors or prostaglandins were blocked. The extract and parthenolide also preserved the antioxidant enzymes superoxide dismutase and catalase and lowered myeloperoxidase activity ^{32Reference 32Ferraz CV et al. · 2026AnimalTanacetum parthenium and parthenolide increase defensive agents and promote antisecretory activity supporting their gastroprotective actions in rodentsView study →}.

This fits the plant’s traditional use for colic, stomach ache and sluggish digestion ^{8Reference 8Pareek et al. · 2011Systematic reviewFeverfew (Tanacetum parthenium L.): A systematic reviewView study →}.

Gap: rodent data only; feverfew has not been tested for stomach or digestive complaints in people.

General tolerance. In the six migraine trials reviewed by Cochrane, side effects were mild and passing, most often stomach upset and mouth ulcers ^{1Reference 1Wider et al. · 2015Systematic reviewFeverfew for preventing migraine — systematic reviewView study →}. In the largest trial, side effects possibly related to treatment occurred in 8.4% on feverfew and 10.2% on placebo ^{2Reference 2Diener et al. · 2005RCTEfficacy and safety of 6.25 mg t.i.d. feverfew CO2-extract (MIG-99) in migraine prevention — randomized, double-blind, placebo-controlled studyView study →}.

Mouth ulcers. Chewing the fresh leaf can inflame the mouth and tongue. In one series of feverfew users, 18% reported side effects, the most serious being mouth ulcers in 11% ^{8Reference 8Pareek et al. · 2011Systematic reviewFeverfew (Tanacetum parthenium L.): A systematic reviewView study →}.

Allergy. Feverfew is contraindicated in anyone allergic to it or to other plants of the daisy family ^{30Reference 30Committee on Herbal Medicinal Products ( · 2020ReviewEuropean Union herbal monograph on Tanacetum parthenium (L.) Schultz Bip., herba — Final, Revision 1 (EMA/HMPC/48715/2017) — regulatory monographView study →}. Its sesquiterpene lactones can cause contact dermatitis: two women developed dermatitis from a moisturiser containing feverfew, and both reacted to daisy-family allergens on patch testing ^{19Reference 19Killoran et al. · 2007Case reportTwo cases of compositae dermatitis exacerbated by moisturizer containing feverfew — case reportView study →}.

Bleeding and blood thinners. Feverfew extracts inhibit platelet aggregation and secretion in the laboratory, and isolated parthenolide acts in the same way ^{10,35Reference 10Heptinstall et al. · 1985In vitroExtracts of feverfew inhibit granule secretion in blood platelets and polymorphonuclear leucocytes — in vitroView study →Reference 35Groenewegen WA · 1990In vitroA comparison of the effects of an extract of feverfew and parthenolide, a component of feverfew, on human platelet activity in-vitro — in vitroView study →}. The EU monograph reports no known interactions ^{30Reference 30Committee on Herbal Medicinal Products ( · 2020ReviewEuropean Union herbal monograph on Tanacetum parthenium (L.) Schultz Bip., herba — Final, Revision 1 (EMA/HMPC/48715/2017) — regulatory monographView study →}, and none has been formally studied. One case report describes a 36-year-old woman taking 800 mg three times a day for nine months who developed vaginal bleeding and a prolonged menstrual cycle, judged probably related to feverfew ^{18Reference 18Alenzi et al. · 2021Case reportAlteration of coagulation test results and vaginal bleeding associated with the use of feverfew (Tanacetum parthenium) — case reportView study →}. Take care alongside anticoagulant or antiplatelet drugs, and stop feverfew before planned surgery ^{18Reference 18Alenzi et al. · 2021Case reportAlteration of coagulation test results and vaginal bleeding associated with the use of feverfew (Tanacetum parthenium) — case reportView study →}.

Drug metabolism. The only data are from the laboratory. In a screen against a mixture of six human CYP enzymes (CYP1A2, 2C8, 2C9, 2C19, 2D6 and 3A4), a feverfew herb extract was among the herbal extracts that inhibited the enzymes, but the published summary does not say which ones ^{37Reference 37Unger M · 2004In vitroSimultaneous 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 — in vitroView study →}. Nothing has been tested in people, and the EU monograph lists no known interactions ^{30Reference 30Committee on Herbal Medicinal Products ( · 2020ReviewEuropean Union herbal monograph on Tanacetum parthenium (L.) Schultz Bip., herba — Final, Revision 1 (EMA/HMPC/48715/2017) — regulatory monographView study →}.

Stopping feverfew. People who switched to placebo after taking feverfew for several years reported headaches, insomnia, nervousness, tiredness and joint and muscle stiffness, often called “post-feverfew syndrome” ^{8Reference 8Pareek et al. · 2011Systematic reviewFeverfew (Tanacetum parthenium L.): A systematic reviewView study →}.

Children. The EU monograph does not recommend feverfew under the age of 18, because there are not enough data ^{30Reference 30Committee on Herbal Medicinal Products ( · 2020ReviewEuropean Union herbal monograph on Tanacetum parthenium (L.) Schultz Bip., herba — Final, Revision 1 (EMA/HMPC/48715/2017) — regulatory monographView study →}.

Quality. Parthenolide content varies widely between plants and with growing conditions, so products differ in what they deliver ^{8,24Reference 8Pareek et al. · 2011Systematic reviewFeverfew (Tanacetum parthenium L.): A systematic reviewView study →Reference 24Bone K · 2013Principles and Practice of Phytotherapy}. Feverfew’s flowers resemble chamomile’s, and the two are sometimes confused ^{8Reference 8Pareek et al. · 2011Systematic reviewFeverfew (Tanacetum parthenium L.): A systematic reviewView study →}.