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 2006.
[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.
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 2006.
[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.
