White Willow with Feverfew by Nature's Answer

POSSIBLY EFFECTIVE

• Migraine headache. Oral feverfew seems to reduce the frequency of migraines and improve migraine-related symptoms. Details: Most clinical research shows that taking feverfew can reduce the frequency of migraine headaches and reduce symptoms of pain, nausea, vomiting, and sensitivity to light and noise (5080,6959,6960,6961,12384,13239,19358,90607). It may be more effective in patients with more frequent migraine attacks (12384). Combination products containing feverfew and other ingredients have also been evaluated, with promising results in most studies (12389,19357,19359,22602,96531,96532,103009,107473). However, some conflicting evidence exists (727,6938,12153,12384). These conflicting findings may reflect differences in the harvested feverfew plants or differences in the bioavailability of commercially prepared feverfew products (12153). Dosing regimens with evidence of benefit include feverfew powder 50-150 mg once daily for up to 4 months (6959,6960,6961,90607) and a carbon dioxide extract of feverfew (MIG-99, Schaper & Brümmer GmbH & Co) 2.08-18.75 mg three times daily for 3 to 4 months (12384,13239).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Prurigo nodularis. It is unclear if topical feverfew is beneficial for patients with this skin condition. Details: Preliminary clinical research in people with prurigo nodularis shows that applying a topical cream containing feverfew (Aveeno Ultra-Calming Cream, Johnson & Johnson) modestly improves pruritus in about 90% of affected patients. However, the cream does not appear to cause complete remission of skin lesions (22601).
• Psoriasis. Although there has been interest in using oral feverfew for psoriasis, there is insufficient reliable information about the clinical effects of feverfew for this purpose.
• Rheumatoid arthritis (RA). It is unclear if oral feverfew is beneficial for patients with RA. Details: Preliminary clinical research in a small number of women with RA shows that taking dried chopped feverfew 70-86 mg daily for 6 weeks does not seem to reduce the symptoms of RA, including pain, stiffness, or grip strength, when compared with placebo (6933).
• Tension headache. Oral feverfew has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Observational research in children and adolescents with tension headache has found that taking a specific combination supplement (Partena) containing feverfew dry extract 150 mg (standardized to 1.2 mg of parthenolides), magnesium 169 mg, coenzyme Q10 20 mg, riboflavin 4.8 mg, and andrographis 100 mg twice daily for 4 weeks and then once daily for 12 weeks is associated with reduced headache frequency, but not pain intensity, when compared to baseline (103009). More evidence is needed to rate feverfew for these uses.

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POSSIBLY EFFECTIVE

• Back pain. Oral willow bark extract has been evaluated for the treatment of back pain, with promising results. Details: Clinical research in patients with chronic low back pain shows that taking a standardized willow bark extract providing salicin 120 mg or 240 mg daily for 4 weeks reduces lower back pain and decreases the need for rescue analgesia when compared with placebo. Salicin 240 mg appears to be more effective than salicin 120 mg, and significant pain relief may be observed after 1 week of high-dose use (6456). Additional research suggests that taking willow bark extract providing salicin 240 mg daily for 4 weeks is as effective as rofecoxib (Vioxx) for lower back pain (12804).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Ankylosing spondylitis. Although there has been interest in using oral willow bark for pain associated with ankylosing spondylitis, there is insufficient reliable information about the clinical effects of willow bark for this purpose.
• Common cold. Although there has been interest in using oral willow bark for common cold symptoms, there is insufficient reliable information about the clinical effects of willow bark for this purpose.
• Dysmenorrhea. Although there has been interest in using oral willow bark for dysmenorrhea, there is insufficient reliable information about the clinical effects of willow bark for this purpose.
• Gout. Although there has been interest in using oral willow bark for gout, there is insufficient reliable information about the clinical effects of willow bark for this purpose.
• Headache. Although there has been interest in using oral willow bark for headache, there is insufficient reliable information about the clinical effects of willow bark for this purpose.
• Influenza. Although there has been interest in using oral willow bark for pain and fever associated with influenza, including swine flu, there is insufficient reliable information about the clinical effects of willow bark for this purpose.
• Joint pain. Oral willow bark has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with joint pain shows that taking capsules of a specific combination product (Instaflex Joint Support, Direct Digital) containing glucosamine sulfate 500 mg, methylsufonlylmethane 167 mg, white willow bark extract 83 mg, ginger root concentrate 17 mg, boswellia extract 42 mg, turmeric root extract 17 mg, cayenne 40 m H.U. 17 mg, and hyaluronic acid 1.3 mg three times daily for 8 weeks reduces joint pain severity by 37% compared to only 16% with placebo. However, the specific combination product does not appear to significantly improve joint stiffness or function when compared with placebo (89560). It is unclear if these findings are due to willow bark, other ingredients, or the combination.
• Myalgia. Although there has been interest in using oral willow bark for myalgia, there is insufficient reliable information about the clinical effects of willow bark for this purpose.
• Obesity. Oral willow bark has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research suggests that willow bark in combination with ephedra and cola nut might cause modest weight loss in overweight and obese people. Willow bark 600 mg daily (containing 90 mg salicin) in divided doses given for 3 months in combination with these central nervous system stimulants might cause a 2 kg reduction in weight (12811). However, this combination may not be appropriate due to safety concerns associated with ephedra. Ephedra is banned in the US due to severe adverse effects (10055).
• Osteoarthritis. Small clinical studies suggest that oral willow bark extract may improve symptoms of osteoarthritis, although some conflicting evidence exists. Details: Some preliminary clinical research in patients with osteoarthritis shows that taking willow bark extract standardized to contain 240 mg of salicin daily for 2 weeks produces moderate analgesic activity when compared with placebo (12474,86490). Additional research shows that taking a specific willow bark extract (Optovit actiFLEX, Hermes Arzneimittel GmbH) standardized to contain salicin 120-240 mg daily for 6 weeks improves swelling, tenderness, and physical function similarly to conventional non-steroidal anti-inflammatory drugs (NSAIDs) (91406). However, other research shows that taking willow bark extract standardized to 240 mg of salicin daily for 6 weeks does not improve pain, stiffness, or physical function when compared with placebo (12475).
• Rheumatoid arthritis (RA). It is unclear if oral willow bark is beneficial in patients with RA. Details: Clinical research in a small number of patients with RA shows that willow bark extract standardized to 240 mg of salicin daily for 6 weeks does not improve pain when compared with placebo (12475). However, it is possible this study was underpowered to detect a significant difference in pain in these patients. More evidence is needed to rate willow bark for these uses.

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LIKELY SAFE ...when used orally and appropriately, short-term. Feverfew has been used safely in studies lasting up to 4 months (6959,6960,6961,13239).

POSSIBLY UNSAFE ...when fresh feverfew leaves are chewed. Chewing raw or unprocessed feverfew leaves can cause oral inflammation, ulceration, swelling of the lips, and sometimes loss of taste (6959).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Feverfew might cause uterine contractions and abortion (12); avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

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POSSIBLY SAFE ...when used orally and appropriately, short-term. Willow bark has been used safely for up to 12 weeks (6456,12474,12475,12804,12811,86473,91406).

CHILDREN: POSSIBLY UNSAFE
when used orally for viral infections. Salicylic acid and aspirin are contraindicated in children with viral infections (12801). Although Reye's syndrome has not been reported, the salicin constituent in willow bark is similar to aspirin and might pose the same risk.

PREGNANCY:
Insufficient reliable information available; avoid using.

LACTATION: POSSIBLY UNSAFE
when used orally. Willow bark contains salicylates which are excreted in breast milk and have been linked to adverse effects in breast-fed infants (12802,12803).

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, feverfew might have additive effects and increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.  Details Laboratory research suggests that feverfew may inhibit platelet aggregation (6935,6936,6942,6943,6944,6945,6951). Additionally, in one case report, a 36-year-old patient taking feverfew 2400 mg daily for 3 months experienced vaginal bleeding and a prolonged menstrual cycle, with a modest increase in partial thromboplastin time (PTT) and prothrombin time (PT) (107472).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, feverfew might increase levels of drugs metabolized by CYP1A2.  Details Laboratory research shows that feverfew might inhibit CYP1A2 (12479). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, feverfew might increase levels of drugs metabolized by CYP2C19.  Details Laboratory research shows that feverfew might inhibit CYP2C19 (12479). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2C8 (CYP2C8) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, feverfew might increase levels of drugs metabolized by CYP2C8.  Details Laboratory research shows that feverfew might inhibit CYP2C8 (12479). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, feverfew might increase levels of drugs metabolized by CYP2C9.  Details Laboratory research shows that feverfew might inhibit CYP2C9 (12479). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, feverfew might increase levels of drugs metabolized by CYP2D6.  Details Laboratory research shows that feverfew might inhibit CYP2D6 (12479). So far, this interaction has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, feverfew might increase levels of drugs metabolized by CYP3A4.  Details Laboratory research shows that feverfew might inhibit CYP3A4 (12479,19361). So far, this interaction has not been reported in humans.

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ACETAZOLAMIDE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, willow bark might result in additive adverse effects associated with acetazolamide.  Details Willow bark contains salicin, a plant salicylate. Human case reports suggests that a combination of acetazolamide and salicylate increases unbound plasma levels of acetazolamide, as well as adverse effects related to acetazolamide (86481).

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, willow bark might increase the risk of bleeding when taken with anticoagulant/antiplatelet drugs.  Details Willow bark has antiplatelet effects, but less so than aspirin (12810).

ASPIRIN Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, willow bark might increase the effects and adverse effects of aspirin.  Details Willow bark contains salicin, a plant salicylate. It might have an additive effect when taken with other salicylate-containing drugs such as aspirin (12808).

CHOLINE MAGNESIUM TRISALICYLATE (Trilisate) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, willow bark might increase the effects and adverse effects of choline magnesium trisalicylate.  Details Willow bark contains salicin, a plant salicylate. It might have an additive effect when taken with other salicylate-containing drugs such as choline magnesium trisalicylate (12808).

SALSALATE (Disalcid) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, willow bark might increase the effects and adverse effects of salsalate.  Details Willow bark contains salicin, a plant salicylate. It might have an additive effect when taken with other salicylate-containing drugs such as salsalate (12808).

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General ...Orally, feverfew is generally well tolerated. Chewing fresh feverfew leaves is more likely to cause mouth ulceration and other adverse effects of the mouth, lips, and tongue when compared with commercial feverfew preparations.
Most Common Adverse Effects:
Orally: Abdominal pain, bloating, constipation, diarrhea, flatulence, heartburn, and nausea. Skin rash may occur in sensitive individuals.
Topically: Dermatitis in sensitive individuals.

Cardiovascular ...Orally, feverfew has been associated with palpitations in one patient in a clinical study (6959).

Dermatologic ...Orally, feverfew can cause skin rash (12383). Topically, allergic contact dermatitis can occur (6958,42856,42891). Allergic reactions to feverfew may be more likely in individuals sensitive to the Asteraceae/Compositae family. Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.

Gastrointestinal ...Orally, feverfew can cause gastrointestinal symptoms such as heartburn, nausea, diarrhea, constipation, abdominal pain and bloating, and flatulence (6938,6959,12383,22602). Oral numbness has also been reported when feverfew has been taken sublingually in combination with ginger (22602). The traditional method of feverfew administration-chewing fresh feverfew leaves-can result in mouth ulceration, inflamed oral mucosa and tongue, swelling of the lips, and occasionally, loss of taste (6935,6959). Mouth ulceration might result from direct contact with feverfew leaves during chewing, possibly attributable to the sesquiterpene lactone constituent (6959). Some researchers suggest that mouth ulceration is a systemic effect, but one study using dried feverfew capsules reported a higher incidence of mouth ulcers in subjects taking placebo than feverfew (6935,6959,6960).

Genitourinary ...Orally, feverfew has been associated with menstrual changes in one patient in a clinical study (6959) and in one case report involving a 36-year-old patient taking 800 mg of feverfew three times daily for 3 months (107472).

Immunologic ...Orally and topically, feverfew may cause an allergic reaction in individuals sensitive to the Asteraceae/Compositae family. Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.

Musculoskeletal ...Orally, feverfew has been associated with joint stiffness in two patients in a clinical study (6959). Discontinuation of oral feverfew after long-term use may cause "post-feverfew syndrome", which includes symptoms such as muscle and joint stiffness (6959,12153).

Neurologic/CNS ...Discontinuation of oral feverfew after long-term use may cause "post-feverfew syndrome", which includes symptoms such as anxiety, headaches, and insomnia (6959,12153).

Other ...Orally, feverfew may cause weight gain (12383).

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General ...Orally, willow bark seems to be well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, dyspepsia, heartburn, and vomiting. May cause itching and rash in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Gastrointestinal bleeding and renal impairment. May cause serious allergic reactions, including anaphylaxis, in people who are allergic to aspirin.

Cardiovascular ...In one clinical trial, a single patient withdrew from the study investigating oral willow bark due to blood pressure instability that the authors determined was 'possibly' related to treatment (12804).

Dermatologic ...Orally, willow bark may cause itching and rash in some people due to allergy (6456,12474,12475,12804,86459).

Gastrointestinal ...Orally, willow bark extract can cause gastrointestinal adverse effects, but these appear to be less frequent than those caused by NSAIDs. Examples include diarrhea, heartburn, vomiting, and dyspepsia (12474,12475,12804,86459). In a case report of a child, severe gastrointestinal bleeding occurred following use of a specific syrup (FreddoBaby), which contained ribwort plantain, licorice, willow bark, black elder, meadowsweet, and propolis. The adverse effect was attributed to salicylate content of the syrup. This product has since been withdrawn from the market (86477).

Immunologic ...Orally, willow bark may cause serious allergic reactions, including anaphylaxis, in people who are allergic to aspirin (10392)

Neurologic/CNS ...Orally, willow bark may cause headache and dizziness (12804). In a clinical trial evaluating a combination product containing willow bark, black cohosh, sarsaparilla, poplar bark, and guaiac wood (Reumalex), severe headaches occurred (35946).

Ocular/Otic ...Orally, symptoms of allergy to willow bark have included swollen eyes (6456).

Renal ...Salicylates can inhibit prostaglandins, which can reduce renal blood flow (12805). Salicin can cause renal papillary necrosis (12806). The risk for toxicity is greater with high acute doses or chronic use (12805).

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