Feverfew Benefits and
Side Effects
Side Effects
Feverfew is popular with its antipyretic properties. It is one of the most commonly used
herbs for helping migraine headache. Some studies have shown its benefits on
inflammation and some vascular issues. It is relatively safe [5]; side effects include skin
rash, mouth ulceration and inflammation. [8] Because of its inhibitory effect on platelet
aggregation, overdose may lead to bleeding. Do not use Feverfew together with
anti-coagulants or blood thinners particularly ginkgo biloba, ginseng and certain plant
oils etc.
Potential Health Benefits of Feverfew
Migraine headache prevention
Feverfew is often taken by mouth for the prevention of migraine headaches. Laboratory
studies show that feverfew 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 combination of feverfew and ginger relieved
migraine of 82% of the subjects. [3]
However, there are also trials not convincingly establish that feverfew is efficacious for
preventing migraine. [6] The inconsistent results may be related to the hug variation in the
parthenolide or other active ingredient content in the feverfew products. Researchers from
Oklahoma State University found parthenolide content per dosage form varied 150-fold
(from 0.02 to 3.0 mg) in some products. If a person consumed the daily dose
recommended on the label, 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 use good quality Feverfew supplements.
Feverfew ingredient has 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 ingredient may benefit patients suffered from rheumatoid arthritis...no
support.
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.
Feverfew extracts show potential anti-cancer benefits in test-tube studies.
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 extracts has anti-platelet aggregation properties.
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]
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 2008.
[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.
herbs for helping migraine headache. Some studies have shown its benefits on
inflammation and some vascular issues. It is relatively safe [5]; side effects include skin
rash, mouth ulceration and inflammation. [8] Because of its inhibitory effect on platelet
aggregation, overdose may lead to bleeding. Do not use Feverfew together with
anti-coagulants or blood thinners particularly ginkgo biloba, ginseng and certain plant
oils etc.
Potential Health Benefits of Feverfew
Migraine headache prevention
Feverfew is often taken by mouth for the prevention of migraine headaches. Laboratory
studies show that feverfew 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 combination of feverfew and ginger relieved
migraine of 82% of the subjects. [3]
However, there are also trials not convincingly establish that feverfew is efficacious for
preventing migraine. [6] The inconsistent results may be related to the hug variation in the
parthenolide or other active ingredient content in the feverfew products. Researchers from
Oklahoma State University found parthenolide content per dosage form varied 150-fold
(from 0.02 to 3.0 mg) in some products. If a person consumed the daily dose
recommended on the label, 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 use good quality Feverfew supplements.
Feverfew ingredient has 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 ingredient may benefit patients suffered from rheumatoid arthritis...no
support.
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.
Feverfew extracts show potential anti-cancer benefits in test-tube studies.
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 extracts has anti-platelet aggregation properties.
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]
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 2008.
[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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EGCG
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Fish Oil
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