feverfew side effects and feverfew benefits
feverfew uses and feverfew migraine updated on August 17, 2011
Feverfew Herb Uses - Abstract
Feverfew is popular with its antipyretic properties. It is one of the most commonly used herbs for helping
migraine headache. Some studies have shown
feverfew benefits on inflammation and some vascular issues.
Feverfew herb is relatively safe [5]; its side effects include skin rash, mouth ulceration and inflammation. [8]
Because of feverfew's inhibitory effect on platelet aggregation, overdosage of feverfew may lead to bleeding.
Do not use Feverfew together with anti-coagulants or blood thinners particularly
ginkgo biloba, ginseng and
certain plant oils etc.

Feverfew Benefits

feverfew migraine
Feverfew is often taken by mouth for the prevention of migraine headaches. Laboratory studies show that
feverfew herb can reduce inflammation and prevent blood vessel constriction (squeezing) that may lead to
headaches. German researchers recruited 170 patients to study the efficacy and tolerability of a CO
(2)-extract of Feverfew on migraine. This randomized, double-blinded, 20-week-study indicated that the
Feverfew extract decreased the migraine frequency. [2]

An open-label study of 30 patients showed a herbal combination of feverfew and ginger relieved migraine of
82% of the subjects.  [3] However, there are also trials giving non-promising results. [6] The inconsistency of its
benefits may be related to the content variations in the feverfew products. Researchers from Oklahoma State
University found that parthenolide content per feverfew products varied 150-fold (from 0.02 to 3.0 mg) in their
study. Consequently, a person consumed the recommended daily dosage, his or her intake of dried feverfew
leaf would range from 225 to 2246 mg/day, a 10-fold variation, while intake of parthenolide would range from
0.06 to 9.7 mg/day, a 160-fold variation. [9] So, we should select good quality feverfew supplements.

Feverfew benefits - anti-inflammatory effects.
Researchers from Yale University noticed that parthenolide targets kinase complex provides a possible
molecular basis for the anti-inflammatory properties of parthenolide, i.e. Feverfew extracts. [19]

Feverfew benefit - on rheumatoid arthritis?
Feverfew, reputed by folklore to be effective in arthritis, has in vitro properties that could be beneficial in the
control of inflammatory disease. Researchers from City Hospital, Nottingham did not find any apparent health
benefit in patients suffered rheumatoid arthritis from their oral Feverfew capsules. Note, they used "chopped
dried feverfew capsules" not proper feverfew extracts, thus, the active ingredients might not be released during
the study. [18] Thus, it is still not clear if feverfew extracts benefit patients suffered from rheumatoid arthritis
symptoms such as joint stiffness or pain. ((By the way, feverfew tea is getting popular.))

Feverfew extracts benefits - anti-cancer effects
Researchers at Clemson University demonstrated the anti-cancer effects of Feverfew extracts on two human
breast cancer cell lines (Hs605T and MCF-7) and one human cervical cancer cell line (SiHa). Among the tested
constituents of feverfew (i.e., parthenolide, camphor, luteolin, and apigenin), parthenolide showed the highest
inhibitory effect. [1]

As discussed, parthenolide, derived from Feverfew, has also been shown to preferentially induce acute
myelogenous leukaemia stem cells to undergo apoptosis. Importantly, parthenolide had no discernable effect
on normal blood cells. Thus, this naturally occurring agent may provide new avenues of investigation for the
treatment of leukaemia. [4]

Parthenolide was tested on two tumor cell lines- mouse fibrosarcoma (MN-11) and human lymphoma (TK6) cell
for its ability to inhibit cell growth. At concentrations above 5.0 microM and an exposure time of 24 h,
parthenolide inhibited cell growth in an irreversible fashion. [10]

Feverfew benefits - anti-platelet aggregation effects.
Feverfew may have antithrombotic potential in addition to its claimed benefit in fever, migraine and arthritis.
[14] Feverfew extracts were found to inhibit ADP, thrombin, or collagen-induced aggregation of human
platelets. The pharmacological properties of feverfew may be due to an inhibitor of cellular phospholipases,
which prevents release of arachidonic acid in response to appropriate physiological stimuli. [11-12] Do not take
feverfew together with aspirin, ginkgo biloba or other blood-thinning agents.

Feverfew extract was also found to inhibit the deposition of platelets on both collagens of type III and IV in a
dose-dependent way. Similar concentrations of extract were needed to inhibit the formation of surface-bound
aggregates and to inhibit platelet spreading in both platelet-rich plasma and gel-filtered platelets. [13]

UK researchers suggested inhibition of platelet behavior is via neutralization of sulphydryl groups either inside
or outside the cell. And, they believed the active components for such activities to be sesquiterpene lactones
such as parthenolide. [15]

Feverfew extract shows benefits of vascular protection.
As discussed in last section, Feverfew extracts inhibit platelet aggregation and secretion of granular contents
from platelets and other cells. They also modify the interaction of platelets with collagen substrates: feverfew
extracts inhibit both platelet spreading and formation of thrombus-like platelet aggregates on the collagen
surface. Russian researchers investigated the effect of an extract of feverfew on the vessel wall using rabbit
aortas that were perfused with a physiological salt solution in-situ. Addition of feverfew extract to the perfusion
medium protected the endothelial cell monolayer from perfusion-induced injury and led to a reversible increase
in the cAMP content of aorta segments. [16]

However, researchers from King's College, UK, have different opinion. They prepared Feverfew leaf extracts
(Tanacetum parthenium) using chloroform, and they found these extracts strongly inhibited responses of rabbit
aortic rings to phenylephrine, 5-hydroxytryptamine, thromboxane mimetic U46619 (9,11-dideoxy-11 alpha,9
alpha-epoxy-methano-PGF2 alpha), and angiotensin II, but the inhibition to contractions induced by potassium
depolarization was much less. The inhibition was concentration- and time-dependent, non-competitive, and
irreversible.

They also noticed that the feverfew extracts also caused a progressive loss of tone of pre-contracted aortic
rings and appeared to impair the ability of acetylcholine to induce endothelium-dependent relaxations of the
tissue. Thus,
Feverfew extracts may induce a serious side or toxic effect to the vasculature. [17]

THIS ARTICLE CAN BE USED AS REFERENCE ONLY. YOU SHOULD CONSULT WITH YOUR DOCTOR FOR ANY QUESTIONS. ALL RIGHTS
RESERVED ZHION 2011.

[1] Wu C, et al, Antiproliferative activities of parthenolide and golden feverfew extract against three human cancer cell lines. J Med Food. 2006
Spring;9(1):55-61. [2] Diener HC, et al, Efficacy and safety of 6.25 mg t.i.d. feverfew CO2-extract (MIG-99) in migraine prevention--a randomized,
double-blind, multicentre, placebo-controlled study. Cephalalgia. 2005 Nov;25(11):1031-41. [3] Cady RK, et al, Gelstat Migraine (sublingually
administered feverfew and ginger compound) for acute treatment of migraine when administered during the mild pain phase. Med Sci Monit. 2005
Sep;11(9):PI65-9. Epub 2005 Aug 26. [4] Guzman ML, et al, Feverfew: weeding out the root of leukaemia. Expert Opin Biol Ther. 2005
Sep;5(9):1147-52. [5] Curry EA 3rd, Phase I dose escalation trial of feverfew with standardized doses of parthenolide in patients with cancer. Invest
New Drugs. 2004 Aug;22(3):299-305. [6] Pittler MH, Feverfew for preventing migraine. Cochrane Database Syst Rev. 2004;(1):CD002286. [8] Paulsen
E, et al, Do monoterpenes released from feverfew (Tanacetum parthenium) plants cause airborne Compositae dermatitis? Contact Dermatitis. 2002
Jul;47(1):14-8. [9] Nelson MH, et al, Variations in parthenolide content and daily dose of feverfew products. Am J Health Syst Pharm. 2002 Aug
15;59(16):1527-31. [10] Ross JJ, et al, Low concentrations of the feverfew component parthenolide inhibit in vitro growth of tumor lines in a
cytostatic fashion. Planta Med. 1999 Mar;65(2):126-9. [11] Makheja AN, et al, A platelet phospholipase inhibitor from the medicinal herb feverfew
(Tanacetum parthenium). Prostaglandins Leukot Med. 1982 Jun;8(6):653-60. [12] Heptinstall S, et al, Extracts of feverfew inhibit granule secretion in
blood platelets and polymorphonuclear leucocytes. Lancet. 1985 May 11;1(8437):1071-4. [13] Losche W, et al, An extract of feverfew inhibits
interactions of human platelets with collagen substrates. Thromb Res. 1987 Dec 1;48(5):511-8. [14] Loesche W, et al, Feverfew--an antithrombotic
drug? Folia Haematol Int Mag Klin Morphol Blutforsch. 1988;115(1-2):181-4. [15]  Heptinstall S, et al,  Inhibition of platelet behaviour by feverfew: a
mechanism of action involving sulphydryl groups. Folia Haematol Int Mag Klin Morphol Blutforsch. 1988;115(4):447-9. [16] Voyno-Yasenetskaya TA,
et al, Effects of an extract of feverfew on endothelial cell integrity and on cAMP in rabbit perfused aorta. J Pharm Pharmacol. 1988 Jul;40(7):501-2.
[17] Barsby RW, et al, Feverfew extracts and parthenolide irreversibly inhibit vascular responses of the rabbit aorta. J Pharm Pharmacol. 1992
Sep;44(9):737-40. [18] Pattrick M, et al, Feverfew in rheumatoid arthritis: a double blind, placebo controlled study. Ann Rheum Dis. 1989
Jul;48(7):547-9. [19] Kwok BH, et al, The anti-inflammatory natural product parthenolide from the medicinal herb Feverfew directly binds to and
inhibits IkappaB kinase. Chem Biol. 2001 Aug;8(8):759-66.
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