Feverfew plant grows widely across Europe and North America. The leaves have been historically used for the therapy of fever and more recently migraine headaches. For centuries, healers relied on the feathery green leaves to treat headaches, stomach upset, rheumatoid arthritis, and menstrual problems. The bright yellow and white blossoms of this flower emit a powerful aroma that was once thought to purify the air and prevent disease. Feverfew herb has also long been used in gardens to repel bees and various insects. And as its common name suggests, it was once popular for reducing fever. Feverfew herb was somewhat forgotten, however, until the late 1970s. That's when migraine sufferers started talking about the potential of feverfew herb to ward off headaches.
 

What's in the herb?
Feverfew herb contains a range of compounds known as sesquiterpene lactones. Over 85% of these are a compound called parthenolide. The active ingredient in feverfew extract, parthenolide, specifically binds to and inhibits a protein which plays a role in the body's inflammatory process. Fever is part of the body's inflammatory response, and inflammation contributes to a range of ailments, including migraines. Parthenolide helps prevent excessive clumping of platelets and inhibits the release of certain inflammatory chemicals. Feverfew's active ingredient parthenolide specifically binds to and inhibits the protein IKK-beta, which plays a role in the body's inflammatory process. Fever is part of the body's inflammatory response, and inflammation contributes to a range of medical diseases, including migraines.

Feverfew extract dosage
The routine dosage of feverfew extract is 100 to 300 mg up to three times a day.  Feverfew extract is sold by herb and raw ingredient suppliers as 0.2 percent parthenolide, to 0.4 percent parthenolide, 0.5 percent parthenolide and 0.6 percent parthenolide..

Feverfew side effects
Since feverfew extract may potentially thin the blood, caution should be taken if you are on coumadin, aspirin, or blood thinners. No major side effects have been reported in the medical literature as of 2012.

Review
Results of studies with feverfew extract in the therapy or prevention of migraine headaches have not been consistent. It appears that a small percentage of users may benefit from feverfew, but a good portion of users may not find this herb helpful.
   The feverfew extract dosage is about 100 to 150 mg of the freeze-dried powdered herb, containing at least 0.4% parthenolide, taken twice a day. Benefits may be noticed within a month or two. Exercise, B vitamins, and magnesium supplements may also help. Some migraine sufferers also notice benefits from a low gluten diet.

Feverfew migraine research
As with any herb or medicine, there are some people who notice a benefit while others don't. It may be worthwhile to give feverfew extract a chance for about 6 to 8 weeks to see if it helps relieve symptoms of migraine.

Efficacy and safety of 6.25 mg t.i.d. feverfew extract MIG-99 in migraine prevention--a randomized, double-blind, multicentre, placebo-controlled study.
Cephalalgia. 2005.
The efficacy and tolerability of feverfew extract (MIG-99, 6.25 mg t.i.d. three times a day) for migraine prevention were investigated. Patients suffering from migraine according to International Headache Society criteria were treated for 16 weeks after a 4-week baseline period. The migraine frequency decreased from 4.7 by 1.9 attacks per month in the MIG-99 group and by 1.3 attacks in the placebo group. Adverse events possibly related to study medication were 9/107 (8%) with feverfew and 11/108 (10%) with placebo. Feverfew is effective and shows a favourable benefit-risk ratio.
     A stable extract of the popular herbal remedy feverfew, called MIG-99, appears to be particularly effective in preventing migraine, German researchers report in the November 2005 issue of Cephalagia. Feverfew herb has traditionally been used to treat migraine, and clinical trials of the powdered herb have shown promising results. However, tests using extracts of feverfew have been less successful. To evaluate feverfew, the researchers conducted a trial with 170 migraine patients. At the beginning of the trial, migraine frequency was approximately five attacks over a 4-week period. The subjects were then randomly assigned to treatment with feverfew, three times a day or to placebo, or "sugar pill," for up to 16 weeks. In the feverfew treatment group, migraine frequency declined by two attacks per month. In the placebo patients, the corresponding decrease was only one per month. Possible medication-related adverse events occurred in about 8 percent of feverfew patients and 10 percent of placebo patients. Further analysis of responder rates revealed that feverfew was 3.4-times more effective than placebo.

A combination of riboflavin, magnesium, and feverfew for migraine prophylaxis: a randomized trial.
Headache 2004.
Randomized double-blind placebo-controlled trial of a compound providing a daily dose of riboflavin 400 mg, magnesium 300 mg, and feverfew 100 mg. The placebo contained 25 mg riboflavin. Forty-nine patients completed the 3-month trial. For the primary outcome measure, a 50% or greater reduction in migraines, there was no difference between feverfew and "placebo" groups. Similarly, there was no significant difference in secondary outcome measures. Compared to baseline, however, both groups showed a significant reduction in number of migraines. This effect exceeds that reported for placebo agents in previous migraine trials. Riboflavin 25 mg showed an effect comparable to a combination of riboflavin 400 mg, magnesium 300 mg, and feverfew 100 mg. The placebo response exceeds that reported for any other placebo in trials of migraine prophylaxis, and suggests that riboflavin 25 mg may be an active comparator. There is at present conflicting scientific evidence with regard to the efficacy of feverfew and these compounds for migraine prophylaxis.

Feverfew for preventing migraine.
Cochrane Database Syst Rev. 2004.
To systematically review the evidence from double-blind randomised controlled trials assessing the clinical efficacy and safety of feverfew versus placebo for preventing migraine. Trials using clinical outcome measures were included. Trials focusing exclusively on physiological parameters were excluded. There were no restrictions regarding the language of publication. Data on patients, interventions, methods, outcome measures, results and adverse events were extracted systematically.  Two reviewers independently selected studies, assessed methodological quality and extracted data. Disagreements concerning evaluation of individual trials were resolved through discussion. Five trials (343 patients) met the inclusion criteria. Results from these trials were mixed and did not convincingly establish that feverfew is efficacious for preventing migraine. Only mild and transient adverse events were reported in the included trials. It appears from the data reviewed that feverfew presents no major safety problems.

The efficacy and safety of Tanacetum parthenium in migraine prophylaxis -- a double-blind, multicentre, randomized placebo-controlled dose-response study.
Cephalalgia 2002.
The clinical efficacy and safety of three dosages of MIG-99 (2 mg; 6.25 mg; 18.75 mg t.i.d.) were compared with placebo. The patients suffered from migraine with and without aura according to International Headache Society (IHS) criteria and were treated with one of the study medications for 12 weeks after a 4-week baseline period. The primary efficacy parameter was the number of migraine attacks during the last 28 days of the treatment period compared with baseline. Secondary endpoints were total and average duration and intensity of migraine attacks, mean duration of the single attack, number of days with accompanying migraine symptoms, number of days with inability to work due to migraine as well as type and amount of additionally taken medications for the treatment of migraine attacks. The design of the study included a pre-planned adaptive interim analysis for patients with at least four migraine attacks within the baseline period. With respect to the primary and secondary efficacy parameter, a statistically significant difference was not found between the overall and the confirmatory intention-to-treat (ITT) sample in the exploratorily analysed four treatment groups. The frequency of migraine attacks for the predefined confirmatory subgroup of patients with at least four migraine attacks during the baseline period decreased in a dose-dependent manner. The highest absolute change of migraine attacks was observed under feverfew treatment with 6.25 mg t.i.d. compared with placebo. Overall, 52 of 147 (35%) patients reported at least one adverse event (AE). The incidence of AEs in the feverfew treatment groups was similar to that in the placebo group, and no dose-related effect was observed in any safety parameter. MIG-99 failed to show a significant migraine prophylactic effect in general. Accordingly, in the ITT analysis a dose-response relationship could not be observed. MIG-99 was shown to be effective only in a small predefined subgroup of patients with at least four attacks during the 28-day baseline period where the most favourable benefit-risk ratio was observed with a dosage of three capsules of 6.25 mg MIG-99 extract per day. Because of the low number of patients, these findings need to be verified in a larger sample. The incidence of AEs was similar for all treatment groups.

Feverfew extract and leukemia research
Parthenolide, a chemical derived from the feverfew plant, destroys acute myeloid leukemia (AML) cells, leaving normal bone marrow cells relatively unscathed. Moreover, the compound may get at the root of the disease because it also kills stem cells that give rise AML.

Feverfew extract and cancer
Suppressed NF-{kappa}B and sustained JNK activation contribute to the sensitization effect of parthenolide to TNF-{alpha}-induced apoptosis in human cancer cells.
Carcinogenesis. 2004.
Parthenolide is the main sesquiterpene lactone found in feverfew with potent anti-inflammatory function. The anticancer property has been demonstrated in both in vitro cell culture and in vivo animal model, while the molecular mechanisms remain to be further elucidated.

Phase I dose escalation trial of feverfew with standardized doses of parthenolide in patients with cancer.
Invest New Drugs. 2004.
A Phase I trial was conducted to evaluate the pharmacokinetics and toxicity of parthenolide given as a component of feverfew (Tanacet trade mark ) administered as a daily oral tablet in a 28-day cycle. A starting dose of 1 mg per day was explored with subsequent dose escalations to 2, 3, and 4 mg. Patients were evaluated for response after every two cycles. Feverfew extract given on this schedule had no significant toxicity, and the maximum tolerated dose was not reached. When parthenolide was administered at doses up to 4 mg as a daily oral capsule in the feverfew preparation, there was not detectable concentration in the plasma. Because of this, parthenolide pharmacokinetics were not able to be completed. Feverfew extract, with up to 4 mg of parthenolide, given daily as an oral tablet is well tolerated without dose-limiting toxicity, but does not provide detectable plasma concentrations. Purification of parthenolide for administration of higher doses will be needed.

Bioactive flavonoids of Tanacetum parthenium revisited.
Phytochemistry. 2003.
Bio-guided fractionation of an extract from feverfew showing activity as mitotic blocker allowed the isolation and identification of santin, jaceidin and centaureidin.

Leukemia
Rep Biochem Mol Biol. 2016. Parthenolide Induces Apoptosis in Committed Progenitor AML Cell line U937 via Reduction in Osteopontin.

Feverfew extract as anti-inflammatory substance
The Yale team found that feverfew's active ingredient -- parthenolide -- specifically binds to and inhibits the protein IKK-beta, which plays a role in the body's inflammatory process. Fever is part of the body's inflammatory response, and inflammation contributes to a range of ailments--including migraines. 100 to 300 mg up to qid, 0.2 to 0.4% parthenolide.

J Dermatol Sci. 2013 Dec. A purified Feverfew extract protects from oxidative damage by inducing DNA repair in skin cells via a PI3-kinase-dependent Nrf2/ARE pathway.

Pain relief
Phytomedicine. 2015. Widespread pain reliever profile of a flower extract of Tanacetum parthenium. Tanacetum parthenium L., commonly called Feverfew, is known for anti-inflammatory and anti-migraine properties. Aimed to individuate new therapeutical strategies to control acute and persistent pain induced by different origins we tested two hydroalcoholic extracts obtained from Feverfew flowers and leaves, respectively. Extracts were characterized according to the European Pharmacopoeia monograph. Both the extracts were tested after acute per os administration in the dose range 30-1000 mg kg(-1). The anti-nociceptive properties were evaluated by the Writhing test in mice. The present Feverfew flower extract behaves as a potent pain reliever in acute, inflammatory, articular and neuropathic pain. It appears as a natural strategy potentially suitable for the treatment of different kinds of pain.