Comprehensive Guide to Feverfew

Feverfew Quick GuideDr. James Meschino DC, MS, ND
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General Features
Feverfew is a member of the sunflower family with the richest source of active constituents found within its leaves. The leaves of the plant contain a unique group of sesquiterpene lactones (85% of which is parthenoloide), which some studies suggest are its primary bioactive agent. Feverfew supplementation has demonstrated an ability to help reduce the frequency, and severity of migraine headaches is some individuals and this is its best-known therapeutic application for which it has gained immense popularity.
Principle Active Constituents

Parthenolide has been considered the primary active constituent, although one study showed that a high parthenolide-yielding supplement was no more effective than a placebo tablet, in a Dutch study of 50 migraine sufferers. This study has cast some doubt as to what bioactive agent present in Feverfew is the one that provides migraine prevention and relief. As such, some authorities suggest using a whole herb Feverfew supplement rather than one that is standardized to yield a high level of parthenolide. Parthenolide represents 85% of the sesquiterpene lactone content of Feverfew , which are the most unique bioactive agents discovered thus far in the leaf of the plant.

Clinical Application and Mechanism of Action
1.Migraine headaches
Feverfew extracts inhibit the manufacture of compounds that promote inflammation, including prostaglandins, leukotrienes, and thromboxanes at the initial stages of a migraine headache, in a similar fashion as cortisone (inhibits phospholipase enzymes not the cyclo-oxygenase enzyme). As such, it blocks the first step of prostaglandin and related eicosanoid synthesis, which involves the activation of fatty acids from the cell membrane phospholipid structure. Due to this action, Feverfew also inhibits platelet aggregation, and vasoconstriction by limiting the synthesis of other eicosanoids such as thromboxane A2. All of these physiological outcomes may help to abort migraine headaches and contains other inflammatory conditions (i.e., arthritis, fever).
A number of well-designed clinical trials have demonstrated that Feverfew supplementation can reduce the frequency of migraine headaches if taken on a preventive basis each day by migraine sufferers. The Nottingham trial involving 59 migraine patients showed a 24% reduction in number of migraine headaches in an eight-month placebo-controlled crossover trial. 4 The clinical studies by Palevitch et al, and Prusinki et al, also demonstrated success in reducing migraine frequency in human subjects with a strong history of migraine headaches. 8, 9 As noted above, a Dutch study reported no benefit from the use of a Feverfew extract over placebo tablets in migraine sufferers. 7 A recent review in the Cochrane Database Systematic Review, by Pittler et al, concludes that the majority of trials suggest a beneficial effect of Feverfew compared with placebo, but the efficacy of Feverfew for the prevention of migraine has not been established beyond a reasonable doubt.
2. Rheumatoid arthritis
Due to its anti-inflammatory effects, the traditional use of Feverfew has also included the management of rheumatoid arthritis. A double-blind study testing this application provided encouraging results, however this should be regarded as preliminary evidence only.
Dosage and Standardized Grade
Migraine Prevention and Maintenance: 25 - 75 mg of Feverfew , taken two to three times per day.
To Abort a Migraine Attack: 1,000 - 2,000 mg may be necessary at the onset of an acute attack.
Arthritis: Clinical trials have used a daily dosage of 76 mg of Feverfew.
Based upon some evidence, using a standardized grade containing capsules or tablets with a parthenolide concentration of 0.4 to 0.7 % may be a consideration. As such, the daily dosage of parthenolide should yield at least 250 mcg.

Adverse Side Effects, Toxicity and Contraindications
Among the many thousands of English citizens who commonly use Feverfew for the above stated medicinal purposes, there have been no reports of serious toxicity, which is also supported by animal experiments. 12 At recommended levels of intake Feverfew extract may produce minor side effects, such as gastrointestinal upset and nervousness in a small percentage of patients.
Parthenolide exhibits anti-platelet clotting properties and can potentially lead to a bleeding disorder in patients with a history of capillary or vascular fragility. As such, it should be use with caution in these individuals.
Chewing the leaves of the Feverfew plant may result in apthous ulcerations or exudative dermatitis from external contact, in sensitive individuals.

Drug-Nutrient Interactions
Anticoagulant Medications (e.g., coumadin, warfarin) - Feverfew may potentiate the anti-clotting effects of these drugs, increasing the risk of a bleeding disorder. Thus, appropriate patient monitoring of prothrombin time (INR) must accompany the concurrent use of Feverfew and anti-coagulant medications.
Pregnancy and Lactation
During pregnancy and lactation, the only supplements that are considered safe include standard prenatal vitamin and mineral supplements. All other supplements or dose alterations may pose a threat to the developing fetus and there is generally insufficient evidence at this time to determine an absolute level of safety for most dietary supplements other than a prenatal supplement. Any supplementation practices beyond a prenatal supplement should involve the cooperation of the attending physician (e.g., magnesium and the treatment of preeclampsia.)

References:Pregnancy and Lactation
1. Encyclopedia of Nutritional Supplements. Murray M. Prima Publishing 1998.
2. Reavley NM. The New Encyclopedia of Vitamins, Minerals, Supplements, and Herbs. Evans and Company Inc. 1998.
3. The Healing Power of Herbs (2nd edition). Murray M. Prima Publishing 1995.
4. Boon H and Smith M. Health Care Professional Training Program in Complementary Medicine. Institute of Applied Complementary Medicine Inc. 1997.
References
1. Heptinstall S, et.al., Parthenolide Content and Bioactivity of Feverfew (Tanaceum Parthenuim (L.) Schultz-Bip), Estimation of Commercial and Authenticated Feverfew Products, J Pharm Pharmacol 44, 1992, 391-395.
2. Heptinstall S, et.al., Extracts of Feverfew Inhibits Granule Secretion in Blood Platelets and Polymorphonuclear Leukocytes, Lancet 1, 1985, 1971-1074.
3. Johnson ES, et.al., Efficacy of Feverfew as Prophylactic Treatment of Migraine, Br Med J 291, 1985, 569-573.
4. Murphy JJ, Heptistall S, and Mitchell JRA, Randomized Double-blind Placebo-controlled Trial of Feverfew in Migraine Prevention, Lancet ii, 1988, 189-192.
5. Pattrick M, et.al., Feverfew in Rheumatoid Arthritis: A Double-blind, Placebo-controlled study, Ann Rheum Dis 48, 1989, 547-549.
6. Murray MT, The Healing Power of Herbs (2nd edition), Prima Publishing, 1995.
7. De Weerdt CJ, Bootsma HRP, Hendricks H. Herbal medicines in migraine prevention. Randomized double-blind, placebo-controlled crossover trial of a feverfew preparation. Phytomedicine. 1996; 3: 225-230.
8. Dietary Supplement Information Bureau. www.content.intramedicine.com: Feverfew
9. Palevitch D, Earon G, Carasso R. Feverfew (Tanacetum parthenium) as a prophylactic treatment for migraine: a double-blind placebo-controlled study. Phytother Res. 1997; 11: 508-511.
10. Pittler MH, Vogler BK, Ernst E. Feverfew for preventing migraine ( Cochrane Review). Cochrane Database Syst Rev. 2000; (3): CDOO2286.
11. Healthnotes, Inc.2001. www.healthnotes.com: Feverfew.
12. Newall C, Anderson LA, Phillpson JD. Herbal Medicines: A Guide for Health-Care Professionals. London, England: Pharmaceutical Press; 1996: 120.
13. McNeill JR. Interactions between herbal and conventional medicines. Can J CME. 1999; 11 (12): 97-110.
14. Groenewegen WA, et al. A comparison of the effects of an extract of feverfew and parthenolide, a component of feverfew, on human platelet activity in-vitro. J Pharm Pharmacol. 1990; 42 (8): 553-57.
15. Biggs MJ, et al. Platelet aggregation in patients using feverfew for migraine. Lancet. 1982; 2 (8301): 776.