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.
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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