Parthenolide is the primary active compound in feverfew (Tanacetum parthenium) that provides anti-inflammatory and pain-relieving benefits, particularly for migraine prevention. Research shows it works by inhibiting inflammatory pathways including NF-ÎşB and prostaglandin synthesis while regulating serotonin release and preventing blood vessel inflammation in the brain. Clinical studies on migraine prevention show mixed results, with some trials demonstrating significant reductions in migraine frequency and severity while others show more modest effects. The most consistent benefits appear in people who experience at least 4 migraines monthly, with regular use potentially reducing attack frequency by 25-30%. Most supplements provide 50-100 mg of standardized feverfew extract containing 0.2-0.4% parthenolide daily, with benefits typically appearing after 4-6 weeks of consistent use. While generally well-tolerated, it may cause mouth ulcers and irritation in some people, and should be avoided by those with bleeding disorders or taking blood thinners. Abrupt discontinuation can sometimes trigger temporary headaches, so gradual tapering is recommended when stopping supplementation.
Alternative Names: Feverfew Extract, Tanacetum parthenium Extract
Categories: Sesquiterpene Lactone, Natural Compound, Anti-inflammatory
Primary Longevity Benefits
- Anti-inflammatory
- Anti-cancer Properties
- Neuroprotection
Secondary Benefits
- Migraine Prevention
- Antioxidant Support
- Cardiovascular Protection
- Pain Relief
Mechanism of Action
Parthenolide is a sesquiterpene lactone compound primarily derived from the feverfew plant (Tanacetum parthenium). Its primary mechanism of action involves inhibition of the NF-ÎşB signaling pathway by preventing the degradation of IÎşB (inhibitor of ÎşB), thereby blocking the nuclear translocation of NF-ÎşB and subsequent pro-inflammatory gene expression. This results in reduced production of inflammatory cytokines, prostaglandins, and leukotrienes. Parthenolide also inhibits 5-lipoxygenase and cyclooxygenase enzymes, further contributing to its anti-inflammatory effects.
Additionally, it demonstrates selective cytotoxicity against cancer cells by increasing reactive oxygen species (ROS), depleting glutathione, and activating JNK (c-Jun N-terminal kinase) pathways, leading to apoptosis. In migraine prevention, parthenolide inhibits serotonin release and platelet aggregation, while also stabilizing vascular smooth muscle.
Optimal Dosage
Disclaimer: The following dosage information is for educational purposes only. Always consult with a healthcare provider before starting any supplement regimen, especially if you have pre-existing health conditions, are pregnant or nursing, or are taking medications.
50-100 mg of standardized feverfew extract containing 0.2-0.4% parthenolide daily
By Condition
| Condition | Dosage | Notes |
|---|---|---|
| Migraine Prevention | 50-100 mg standardized feverfew extract (0.2-0.4% parthenolide) daily | Most clinical studies used this dosage range for migraine prevention |
| Inflammatory Conditions | 100-125 mg standardized feverfew extract daily | May be divided into 2-3 doses throughout the day |
| Cancer Adjunctive Support | Varies based on extract concentration | Should only be used under medical supervision for cancer support |
By Age Group
| Age Group | Dosage | Notes |
|---|---|---|
| Adults | 50-100 mg standardized feverfew extract daily | Start with lower doses and increase gradually if needed |
Bioavailability
Absorption Rate
Moderate oral bioavailability with significant first-pass metabolism
Enhancement Methods
Lipid-based delivery systems, Standardized extracts with higher parthenolide content
Timing Recommendations
Best taken with food to reduce potential gastrointestinal effects
Safety Profile
Safety Rating
Side Effects
- Mouth ulcers and irritation
- Gastrointestinal discomfort
- Allergic reactions (especially in those allergic to plants in the Asteraceae family)
- Taste alterations
- Headaches upon discontinuation (‘post-feverfew syndrome’)
Contraindications
- Pregnancy and breastfeeding
- Bleeding disorders
- Scheduled surgery (discontinue 2 weeks prior)
- Children under 2 years
- Allergies to plants in the daisy family (Asteraceae)
Drug Interactions
- Anticoagulants/antiplatelets (potential increased bleeding risk)
- NSAIDs
- Certain migraine medications
- Immunosuppressants
Upper Limit
No established upper limit; most studies used extracts containing up to 0.4% parthenolide
Regulatory Status
Fda Status
Not approved as a drug; available as a dietary supplement ingredient
International Status
Eu: Feverfew is registered as a traditional herbal medicinal product in some countries
Canada: Health Canada has granted a Drug Identification Number (DIN) for certain feverfew products for migraine prevention
Australia: Listed complementary medicine
Synergistic Compounds
| Compound | Synergy Mechanism | Evidence Rating |
|---|---|---|
| Coenzyme Q10 | Combined effects on migraine prevention through complementary pathways | 2 |
| Magnesium | Enhanced effects on migraine prevention and neurological function | 2 |
| Riboflavin (Vitamin B2) | Complementary effects on mitochondrial function and migraine prevention | 2 |
Antagonistic Compounds
| Compound | Interaction Type | Evidence Rating |
|---|---|---|
| Blood thinners | Potential additive anticoagulant effects increasing bleeding risk | 3 |
| NSAIDs | Potential interference with therapeutic effects of both compounds | 2 |
Cost Efficiency
Relative Cost
medium
Cost Per Effective Dose
$0.30-$1.50 per day for supplements
Value Analysis
Relatively cost-effective for migraine prevention compared to prescription medications; quality and standardization of products vary widely
Stability Information
Shelf Life
1-2 years when properly stored
Storage Recommendations
Store in cool, dry place away from direct sunlight in airtight containers
Degradation Factors
Heat, Light exposure, Moisture, Oxidation
Sourcing
Synthesis Methods
- Extraction from plant material using various solvents
- Semi-synthetic derivatives
Natural Sources
- Feverfew (Tanacetum parthenium) plant, particularly the leaves and flowers
Quality Considerations
Look for standardized extracts with verified parthenolide content (typically 0.2-0.4%); quality can vary significantly between products
Historical Usage
Feverfew, the primary source of parthenolide, has been used medicinally since ancient times. The Greek physician Dioscorides prescribed
it for ‘all hot inflammations.’ The plant earned the name ‘medieval aspirin’ and was traditionally used for fevers (hence the name ‘feverfew’), headaches, arthritis, menstrual problems, and digestive issues. In the 1970s,
it gained renewed attention
when a British patient reported success using feverfew leaves for severe migraine, leading to modern scientific investigation of parthenolide.
Scientific Evidence
Evidence Rating
Key Studies
Meta Analyses
Cochrane review (Pittler & Ernst, 2004) found insufficient evidence to establish efficacy of feverfew for preventing migraine headaches, with mixed results across trials
Ongoing Trials
Clinical trials investigating parthenolide derivatives for cancer treatment, Studies on standardized feverfew extracts for inflammatory conditions
Disclaimer: The information provided is for educational purposes only and is not intended as medical advice. Always consult with a healthcare professional before starting any supplement regimen, especially if you have pre-existing health conditions or are taking medications.