Feverfew: Choosing a Product and Dosing

With most supplements, choosing a product is a matter of price and taste. With feverfew it is arguably the whole question, because the difference between two bottles on the same shelf can be larger than the difference between the herb and a placebo.

That is not rhetoric. When pharmacy researchers bought commercial feverfew products and measured the parthenolide each one delivered at its own recommended daily dose, the range was 0.06 to 9.7 mg per day — a 160-fold difference (Nelson 2002). An earlier analysis using three independent methods found that some products sold as feverfew contained no detectable parthenolide at all (Heptinstall 1992).

So this page is the practical one. What the different forms are, what the numbers on a label mean, which numbers are useless, how the doses used in trials translate, how long to take it, and how to stop.

Table of Contents

1. How Bad the Variability Actually Is
2. The Forms of Feverfew
3. Reading a Feverfew Label
4. The Doses Actually Used in Trials
5. Translating a Trial Dose to a Real Product
6. Why Chewing Fresh Leaves Is a Bad Idea
7. Storage, Shelf Life and Degradation
8. How Long to Take It, and How to Judge
9. Stopping and Tapering
10. Combination Products and Stacking
11. What It Costs and Whether It Is Worth It
12. Cautions and Interactions
13. Key Research Papers
14. Connections

How Bad the Variability Actually Is

Two published analyses define the problem, and both deserve to be read in their own numbers.

Nelson 2002 — the 160-fold finding

Researchers at Southwestern Oklahoma State University's School of Pharmacy bought commercial feverfew products and analysed them by high-performance liquid chromatography (Nelson 2002). What they found:

• The weight of feverfew leaf per capsule broadly matched the label, ranging from 25 to 500 mg. So manufacturers were putting in roughly what they claimed, by weight.
• Parthenolide per dosage form varied 150-fold, from 0.02 mg to 3.0 mg.
• Expressed as a percentage of the material, parthenolide varied 5.3-fold, from 0.14% to 0.74%.
• Following each product's own label directions, daily leaf intake would range from 225 to 2,246 mg (a 10-fold spread) and daily parthenolide intake from 0.06 to 9.7 mg — a 160-fold spread.

The 160-fold figure is the product of two multiplying problems: the herb varies in potency, and the labels recommend very different amounts of it. A consumer following instructions faithfully has no way to know which end of that range they are on.

Heptinstall 1992 — some products had none

An international team measured parthenolide by HPLC, NMR spectroscopy, HPLC of a derivative, and a platelet bioassay. All four methods agreed with each other, so the numbers are trustworthy. Their findings (Heptinstall 1992):

• Authenticated Tanacetum parthenium grown in the UK had high parthenolide in leaves, flowering tops and seeds, and low levels in stalks and roots. What part of the plant goes into the capsule matters.
• Parthenolide levels in powdered leaf fell during storage.
• Purported feverfew products “varied widely in their parthenolide content and in some products parthenolide was not detected.”
• Their recommendation, more than thirty years ago: manufacturers should use parthenolide measurement as a means of standardisation and quality control.

Two further wrinkles worth knowing. Feverfew is occasionally misidentified: Tanacetum vulgare (tansy) and Anthemis or Matricaria species look broadly similar to a non-botanist, and tansy contains thujone, which is genuinely toxic. And because parthenolide degrades, the same bottle is not the same product a year later — a dermatology group re-analysing a feverfew cream after two years found no parthenolide remaining (Paulsen 2010).

The Forms of Feverfew

Reading a Feverfew Label

Six things to look for, in order of how much they tell you.

The single most useful question: can you work out how many milligrams of parthenolide you will swallow per day? If the label does not let you calculate that, you cannot compare the product with any study, and you cannot compare it with the bottle you bought last year. That is the practical meaning of the 160-fold finding.

A worked example. A capsule of 380 mg dried leaf standardised to 0.5% parthenolide contains 380 × 0.005 = 1.9 mg parthenolide. Two capsules daily is 3.8 mg/day — near the top of what the Nelson survey found in real products, and well above the 0.5 mg/day used in the negative Dutch trial. Whether more is better is unproven, but at least you know where you stand.

The Doses Actually Used in Trials

Copy these from the trials, not from the internet:

The commonly quoted range of 50–150 mg of dried leaf per day is a fair summary of the dried-leaf studies. It is not a dose for a CO₂ extract, where 18.75 mg per day was the effective amount — because that is concentrated material, not leaf.

Translating a Trial Dose to a Real Product

Three rules that will keep you out of trouble.

1. Never move a milligram figure between preparations. 18.75 mg of MIG-99 CO₂ extract and 18.75 mg of dried leaf powder are not comparable in any way. Extracts concentrate; leaf does not. Match the number to the form on the label.

2. If your product states parthenolide, use that as the common currency. It is the only figure that means the same thing across preparations. For orientation, the negative Dutch trial delivered 0.5 mg/day; commercial products in the Nelson survey delivered 0.06–9.7 mg/day; the phase I safety trial went to 4 mg/day with no toxicity and no maximum tolerated dose reached (Curry 2004).

3. If your product states nothing useful, treat the dose on the label as arbitrary. It probably is. Follow it, because exceeding a label dose on an unquantified product is worse, but do not imagine you are replicating a trial.

One more honest note. There is no established dose-response relationship for feverfew in humans. The one study designed to find one — Pfaffenrath 2002 — failed to demonstrate it in its main analysis. Higher parthenolide is not proven to be better. It is simply the only variable you can measure.

Why Chewing Fresh Leaves Is a Bad Idea

The traditional British method — two or three fresh leaves in a sandwich each morning — is how feverfew's modern reputation began, and it is the one method we can confidently advise against.

• Mouth ulcers. This is feverfew's signature side effect, and it is overwhelmingly associated with chewing raw leaf. Painful aphthous-type ulcers, a sore or swollen tongue and lips, and sometimes temporary loss of taste. Cochrane's review of the trial data lists mouth ulcers as one of the two most common adverse events reported (Wider 2015). It is the direct local consequence of parthenolide's reactive chemistry meeting mucosal tissue.
• Completely uncontrolled dose. Parthenolide content varies with the plant, the season, the growing conditions and which leaf you pick. Three leaves is not a dose.
• Misidentification risk. Garden plants are not labelled. Tansy (Tanacetum vulgare) contains thujone and is not a substitute.
• Contact dermatitis. Handling the fresh plant can sensitise skin in susceptible people.

Capsules of dried leaf largely bypass the mouth-ulcer problem by not contacting the oral mucosa. If you grow feverfew and like the idea of using it, dry the leaves and encapsulate rather than chew — and accept that you still will not know the dose.

Storage, Shelf Life and Degradation

Parthenolide is chemically reactive, and reactive compounds do not last. The 1992 analysis found parthenolide levels fell during storage of powdered leaf material (Heptinstall 1992), and a feverfew cream re-analysed two years after purchase had no detectable parthenolide left (Paulsen 2010). Formulation work has confirmed that feverfew extract properties relevant to product quality are sensitive to processing and handling (Jin 2008).

Practical consequences:

• Buy small quantities and use them. A year's supply bought on offer is a year's supply degrading in your cupboard.
• Check the expiry date and buy the freshest stock — more meaningful for feverfew than for a mineral supplement, which does not degrade at all.
• Keep it cool, dark and dry. Not above the stove, not on a sunny windowsill, not in a steamy bathroom.
• Keep the desiccant sachet in the bottle and close the lid properly.
• Be suspicious of a product that suddenly seems to stop working. With feverfew, an old bottle is a genuinely plausible explanation.

How Long to Take It, and How to Judge

Feverfew is a preventive. That dictates everything about the schedule.

• Take it every day, whether or not you have a headache. It has never been tested any other way.
• With food is sensible — gastrointestinal upset is the other common mild side effect, and food reduces it.
• Spread the dose if the label says so. The best trial used three times daily.
• Allow 8–12 weeks before deciding. Diener's trial ran 16 weeks and measured the effect during treatment months two and three, deliberately excluding the first month.
• Keep a headache diary starting a month before you begin. Every trial used a 4-week baseline because migraine frequency naturally fluctuates. Without a baseline you will simply misattribute a good month.
• Decide your success criterion in advance — for example, at least two fewer migraine days per month — and write it down.

Set expectations from the actual data: the best trial produced 0.6 fewer attacks per month than placebo. If your realistic hope is “perhaps one fewer attack most months, possibly more if I turn out to be a responder,” feverfew may satisfy you. If your hope is to stop having migraines, it will not.

Stopping and Tapering

This is the part people miss, and it is important enough to have its own name.

Do not stop long-term feverfew abruptly. Regular users who quit suddenly have described a withdrawal cluster — rebound headache often worse than baseline, anxiety, poor sleep, fatigue, and muscle and joint stiffness — known as post-feverfew syndrome. The first controlled trial documented exactly this: habitual users switched to placebo had significantly more frequent and severe headache, nausea and vomiting, with unpleasant effects emerging in the early months (Johnson 1985).

A sensible taper for someone who has been taking it daily for months:

1. Halve the daily dose for one week.
2. Halve again, or move to alternate days, for a second week.
3. Stop.
4. If rebound headache appears, go back up one step and taper more slowly.

Two practical implications. First, if you are stopping feverfew because you think it is not working, taper anyway — otherwise the rebound will convince you it was working after all, for the wrong reason. Second, if you must stop for surgery, plan the taper so it finishes about two weeks before the operation rather than stopping the night before. Details are in Side Effects and Post-Feverfew Syndrome.

Combination Products and Stacking

Feverfew appears in a lot of blends. A few notes:

• Feverfew plus ginger, sublingual. Tested for acute treatment, not prevention. The 2011 pilot in 60 patients treating 221 attacks reported 32% pain-free at two hours versus 16% on placebo (Cady 2011), following a smaller 2005 open study (Cady 2005). Reasonable to try for early treatment; not a substitute for a preventive, and not feverfew alone.
• Feverfew plus willow bark. An open-label uncontrolled study reported benefit (Shrivastava 2006). Open-label, uncontrolled studies of headache remedies routinely look positive and routinely fail when blinded. Also note willow bark is salicylate-based, which compounds the bleeding caution.
• Feverfew in a proprietary “migraine blend.” If the label does not disclose per-ingredient amounts, you cannot know your feverfew dose — and given the variability data, an undisclosed feverfew dose is close to no information at all.
• Stacking with magnesium or riboflavin is common and reasonably safe, but change one thing at a time or you will never know what helped.
• Adding feverfew to a prescription preventive should be a conversation with the prescriber, mainly because of the antiplatelet effect and because your clinician needs to be able to interpret changes in your headache pattern.

What It Costs and Whether It Is Worth It

Feverfew is inexpensive. Basic dried-leaf capsules typically cost a few pounds or dollars a month; a standardised or CO₂ extract is more, but rarely dramatically so. Against a documented net benefit of 0.6 attacks per month in the best trial, and an adverse-event rate no higher than placebo, the risk-benefit arithmetic for a low-cost, well-tolerated preventive is not unreasonable — provided you are honest with yourself about the size of the expected effect and you buy a product whose contents you can quantify.

Where it is not worth it: as a substitute for evaluating frequent or disabling migraine properly; as a reason to postpone effective prescription prophylaxis; or as an unquantified capsule bought purely on price, which is the version of feverfew most likely to be one of the products containing almost no parthenolide.

Cautions and Interactions

• Pregnancy and breastfeeding — avoid. Traditional emmenagogue reputation, and the only experimental reproductive screen (rats, 839 mg/kg) produced smaller fetuses and embryotoxicity in culture, with the authors calling for a full study (Yao 2006). Insufficient data for breastfeeding.
• Asteraceae (Compositae) allergy. Cross-reactivity with ragweed, chrysanthemum, marigold, daisy and chamomile. Parthenolide is a recognised contact sensitiser (Paulsen 2010).
• Anticoagulants and antiplatelet drugs. Feverfew inhibits platelet aggregation and granule secretion (Heptinstall 1985; Groenewegen 1990) and altered platelet responses have been seen in feverfew users (Biggs 1982). Use caution with warfarin, aspirin, clopidogrel, DOACs, and with high-dose fish oil or other antiplatelet supplements.
• Surgery and dental procedures. Stop about two weeks beforehand — tapered, not abruptly — and tell your surgeon and anaesthetist you have been taking it.
• NSAIDs. Long-term concurrent use has been flagged as theoretically undesirable given feverfew's COX-2 inhibiting activity, particularly in people with coronary disease (Saranitzky 2009). No clinical harm has been demonstrated, but it is worth a mention to your doctor.
• Children. Not recommended — not adequately studied. Paediatric migraine should be managed by a clinician.
• Existing mouth ulcers or oral disease. Avoid chewing the leaf entirely; capsules are the safer route.

Key Research Papers

Every identifier was verified live against NCBI E-utilities before being written here.

Product quality, content and stability

1. Nelson MH, Cobb SE, Shelton J. Variations in parthenolide content and daily dose of feverfew products. American Journal of Health-System Pharmacy. 2002;59(16):1527–1531. The 150-fold per-capsule and 160-fold daily-dose findings.
2. Heptinstall S, Awang DV, Dawson BA, Kindack D, Knight DW, May J. Parthenolide content and bioactivity of feverfew: estimation of commercial and authenticated feverfew products. Journal of Pharmacy and Pharmacology. 1992;44(5):391–395. Some products had no detectable parthenolide; levels fell during storage.
3. Jin P, Madieh S, Augsburger LL. Selected physical and chemical properties of feverfew (Tanacetum parthenium) extracts important for formulated product quality and performance. AAPS PharmSciTech. 2008;9(1):22–30.
4. Paulsen E, Christensen LP, Fretté XC, Andersen KE. Patch test reactivity to feverfew-containing creams in feverfew-allergic patients. Contact Dermatitis. 2010;63(3):146–150. Parthenolide undetectable in a cream re-analysed two years later.

The dosing trials

1. Diener HC, Pfaffenrath V, Schnitker J, Friede M, Henneicke-von Zepelin HH. Efficacy and safety of 6.25 mg t.i.d. feverfew CO₂-extract (MIG-99) in migraine prevention. Cephalalgia. 2005;25(11):1031–1041.
2. Pfaffenrath V, Diener HC, Fischer M, Friede M, Henneicke-von Zepelin HH. The efficacy and safety of Tanacetum parthenium (feverfew) in migraine prophylaxis: a dose-response study. Cephalalgia. 2002;22(7):523–532. The dose-response study that did not demonstrate a dose response overall.
3. Murphy JJ, Heptinstall S, Mitchell JR. Randomised double-blind placebo-controlled trial of feverfew in migraine prevention. The Lancet. 1988;2(8604):189–192.
4. De Weerdt CJ, Bootsma HP, Hendriks H. Herbal medicines in migraine prevention: randomized double-blind placebo-controlled crossover trial of a feverfew preparation. Phytomedicine. 1996;3(3):225–230. Alcoholic extract, 0.5 mg parthenolide/day, no effect.
5. Johnson ES, Kadam NP, Hylands DM, Hylands PJ. Efficacy of feverfew as prophylactic treatment of migraine. British Medical Journal (Clinical Research Ed.). 1985;291(6495):569–573.
6. Wider B, Pittler MH, Ernst E. Feverfew for preventing migraine. Cochrane Database of Systematic Reviews. 2015;4(4):CD002286. Mouth ulcers and gastrointestinal complaints listed as the commonest adverse events.

Safety, tolerability and combinations

1. Curry EA 3rd, Murry DJ, Yoder C, et al. Phase I dose escalation trial of feverfew with standardized doses of parthenolide in patients with cancer. Investigational New Drugs. 2004;22(3):299–305. Up to 4 mg parthenolide daily was well tolerated with no dose-limiting toxicity.
2. Heptinstall S, White A, Williamson L, Mitchell JR. Extracts of feverfew inhibit granule secretion in blood platelets and polymorphonuclear leucocytes. The Lancet. 1985;1(8437):1071–1074.
3. Biggs MJ, Johnson ES, Persaud NP, Ratcliffe DM. Platelet aggregation in patients using feverfew for migraine. The Lancet. 1982;2(8301):776.
4. Yao M, Ritchie HE, Brown-Woodman PD. A reproductive screening test of feverfew: is a full reproductive study warranted? Reproductive Toxicology. 2006;22(4):688–693.
5. Cady RK, Goldstein J, Nett R, Mitchell R, Beach ME, Browning R. A double-blind placebo-controlled pilot study of sublingual feverfew and ginger (LipiGesic M) in the treatment of migraine. Headache. 2011;51(7):1078–1086.
6. Cady RK, Schreiber CP, Beach ME, Hart CC. Gelstat Migraine (sublingually administered feverfew and ginger compound) for acute treatment of migraine when administered during the mild pain phase. Medical Science Monitor. 2005;11(9):PI65–PI69. Open-label.
7. Shrivastava R, Pechadre JC, John GW. Tanacetum parthenium and Salix alba (Mig-RL) combination in migraine prophylaxis: a prospective, open-label study. Clinical Drug Investigation. 2006;26(5):287–296.
8. Saranitzky E, White CM, Baker EL, Baker WL, Coleman CI. Feverfew for migraine prophylaxis: a systematic review. Journal of Dietary Supplements. 2009;6(2):91–103.

Live PubMed Searches

1. Feverfew standardisation and parthenolide content
2. Herbal supplement quality and adulteration
3. Supercritical CO₂ extraction of botanicals
4. Parthenolide stability and storage
5. Tansy, thujone and misidentification
6. Feverfew and anticoagulant interactions
7. Herbal medicines and perioperative bleeding
8. Headache diaries in prophylaxis trials

Connections

• All Herbs
• Feverfew Benefits — hub
• Migraine Prevention — what the trials found
• How Parthenolide Works
• Side Effects and Post-Feverfew Syndrome
• Feverfew — the main herb page
• Migraine
• Neurology
• Butterbur — where product quality is a safety issue, not just an efficacy one
• Ginger — the partner herb in sublingual combinations
• Chamomile

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