Feverfew

Parthenolide is the principal bioactive of feverfew. It inhibits NF-κB signalling, suppresses platelet aggregation and serotonin (5-HT) release, inhibits prostaglandin and leukotriene synthesis, and reduces pro-inflammatory cytokine production. These actions underlie the plant's investigated use in migraine prophylaxis.

These related lactones contribute additional anti-inflammatory and smooth-muscle effects and, as α-methylene-γ-butyrolactones, are responsible for the allergic contact dermatitis and mouth-ulceration seen with feverfew.

Lipophilic flavonols such as tanetin and flavones including apigenin and luteolin have antioxidant and anti-inflammatory activity and inhibit prostaglandin synthesis.

The aromatic volatile oil contributes the bitter camphoraceous odour and has mild antimicrobial and spasmolytic activity.

Feverfew leaf contains measurable melatonin, which has been proposed as a possible contributor to effects in some products, though amounts are very small.

Traditionally two to three fresh or dried leaves were chewed daily for migraine and arthritis; chewing frequently causes mouth ulceration and lip swelling, so encapsulated dried leaf standardized to parthenolide (≥0.2%) is now preferred, typically providing about 50-125 mg of leaf daily.

Stabilized supercritical CO2 extract (as MIG-99) was used at 6.25 mg three times daily in controlled migraine trials. Extracts standardized to parthenolide are used for consistent dosing.

A leaf infusion or hydroalcoholic tincture is used in traditional Western herbalism. Feverfew is contraindicated in pregnancy (emmenagogue and uterine-stimulant activity) and in people allergic to Asteraceae (ragweed, chamomile, chrysanthemum). Abrupt discontinuation after long use may cause a 'post-feverfew syndrome' of rebound headache, anxiety and muscle stiffness.

In 170 intention-to-treat migraine patients, a stable supercritical CO2 feverfew extract (MIG-99, 6.25 mg three times daily) for 16 weeks reduced migraine frequency by 1.9 attacks/month versus 1.3 for placebo (p=0.0456), with the greatest benefit in more severely affected patients and a good tolerability profile.

This dose-finding study of a feverfew CO2 extract (2.08, 6.25 and 18.75 mg t.i.d.) did not show a significant difference from placebo in the full analysis, but a pre-defined subgroup with more frequent baseline attacks responded to the 6.25 mg dose, informing the later confirmatory MIG-99 trial.

In 72 patients, dried feverfew leaf (one capsule daily) versus placebo over an 8-month crossover reduced the mean number and severity of migraine attacks and the degree of vomiting, without change in attack duration – an early trial supporting prophylactic benefit.

Greek and Roman writers described 'parthenium', a daisy-like herb used for menstrual and inflammatory complaints; the plant's association with women's ailments persisted in later herbals.

Renaissance English herbals recommended 'feverfew' (from the Latin febrifugia, 'fever-driver') for headaches, fevers, agues and 'all pains in the head', foreshadowing its modern use in migraine.

Hill wrote that feverfew was effective 'in the worst headaches', an early explicit endorsement of its use for severe headache that is often cited in modern reviews.