Allergic Rhinitis and Hay Fever

The claim you will see everywhere is that butterbur works as well as an antihistamine for hay fever without making you drowsy. That claim is not invented — it comes from real randomised trials, published in the BMJ and elsewhere, comparing a standardised butterbur extract head-to-head with cetirizine and with fexofenadine. It is also considerably weaker than it sounds, for a reason that has nothing to do with herbs and everything to do with statistics: proving two treatments are equally good takes far more people than proving one beats a placebo, and these trials were small.

This article walks through each trial with its actual size, reports the negative and mixed results alongside the positive ones, and ends where every butterbur article has to end — with the pyrrolizidine-alkaloid ceiling that sits over the whole subject, and with a botanical irony that matters here more than anywhere else: butterbur is in the same plant family as ragweed.

Table of Contents

1. What Allergic Rhinitis Is, and What Would Count as Working
2. Ze 339: The Extract the Trials Used
3. The Cetirizine Trial
4. The Fexofenadine Trial
5. The Dose-Finding Trial
6. The Scottish Challenge Studies
7. What Independent Reviewers Concluded
8. Asthma: The Weakest Claim
9. Leukotrienes: Why This Might Work
10. Dose, Season Timing and What to Expect
11. The Ragweed Problem
12. Cautions and the Safety Ceiling
13. The Honest Verdict
14. Key Research Papers
15. Connections

What Allergic Rhinitis Is, and What Would Count as Working

Allergic rhinitis is what happens when your immune system decides that grass pollen, tree pollen, ragweed, dust mite or cat dander is a threat. IgE antibodies sitting on mast cells in the lining of your nose recognise the allergen, the mast cells rupture, and out comes a chemical cocktail — histamine first, then leukotrienes and prostaglandins over the following hours.

Those two waves produce different symptoms, which is why different drugs help with different complaints:

• Histamine drives the immediate misery: sneezing, itching, streaming nose, itchy watery eyes. This is what antihistamines block.
• Leukotrienes drive the slower, heavier symptoms: nasal blockage and congestion, swelling of the lining, mucus production. Antihistamines are notably poor at congestion; this is the territory of leukotriene-receptor drugs such as montelukast and of nasal steroids.

Butterbur’s pharmacology points at the second wave, which is a genuinely interesting place for a plant to act. Keep that in mind when reading the trials: an agent that works on leukotrienes should show up most clearly in blockage and congestion scores.

Trials of allergic rhinitis usually report a total nasal symptom score — sneezing, itching, running and blockage each rated on a small scale and added up — plus quality-of-life questionnaires. “Working” means a bigger fall in that score than placebo produces. Placebo produces a lot: people enrol when their symptoms peak, pollen counts move, and everyone improves on the calendar alone.

Ze 339: The Extract the Trials Used

Every positive allergic-rhinitis trial for butterbur used one preparation: Ze 339, marketed as Tesalin, a standardised leaf extract of Petasites hybridus whose tablets are labelled by their petasine content. It is not the same product as the migraine extract, it is not the same plant part, and it is not the same dose schedule.

This matters commercially. A capsule marketed in the United States as “butterbur for allergies” is very often the migraine-style root extract, or an unstandardised extract, sold on the strength of trials conducted with something else. When the research is this narrow — essentially one product, largely one investigator — the gap between “butterbur works” and “this bottle works” is wide enough to drive a truck through. See Choosing a PA-Free Product for how to tell the difference.

The Cetirizine Trial

Schapowal published this in the BMJ in 2002, and it is the study behind nearly every “as good as an antihistamine” headline.

• Design: randomised, double-blind, active-comparator.
• Size: 125 participants with seasonal allergic rhinitis.
• Duration: two weeks.
• Arms: butterbur Ze 339 versus cetirizine.
• Result: both groups improved on quality-of-life and symptom measures, with no significant difference between them. Sedation and fatigue were reported more often in the cetirizine group.

Now the part that usually goes missing. There was no placebo arm. Without one, a trial in which two treatments improve equally cannot distinguish between “both work equally well” and “neither did much and everyone got better anyway.” And 125 people is far too few for an equivalence claim: with that many participants, a real difference of the size that would matter clinically could easily hide inside the statistical noise. “We failed to detect a difference” is not the same statement as “there is no difference,” and small trials fail to detect differences routinely.

The sedation finding is more solid, because it is a within-trial comparison of a known drug effect: cetirizine does cause drowsiness in a minority of users, butterbur apparently does not. If daytime alertness is your problem with antihistamines, that observation is genuinely relevant — though it should be weighed against the second-generation antihistamines that are essentially non-sedating anyway.

The Fexofenadine Trial

The 2005 study in Phytotherapy Research is the stronger design, because it added the missing arm.

• Design: prospective, randomised, double-blind, placebo- and antihistamine-controlled.
• Size: 330 participants with intermittent allergic rhinitis — the largest butterbur rhinitis trial.
• Duration: two weeks.
• Arms: butterbur Ze 339, fexofenadine, placebo.
• Result: both butterbur and fexofenadine improved symptom scores compared with placebo, and were comparable to each other.

This is the single most useful piece of evidence butterbur has in allergy. It is properly blinded, it has a placebo comparator, and 330 people is a respectable size. The remaining limitations are the ones that apply to the whole literature: two weeks is short for a condition people live with for a whole season, and the trial — like all the others — used one proprietary extract with the sponsor’s involvement.

The Dose-Finding Trial

Published in the Archives of Otolaryngology–Head & Neck Surgery in 2004, this study asked whether more extract does more.

• Design: prospective, randomised, double-blind, placebo-controlled.
• Size: 186 participants with intermittent allergic rhinitis.
• Arms: one tablet of Ze 339 three times daily, two tablets three times daily, or placebo.
• Result: a dose-dependent improvement in symptom scores over placebo, with the higher dose performing better.

Dose-response is one of the most persuasive patterns in pharmacology. Placebo effects and biased reporting do not usually produce a neat gradient in which more drug gives more effect; real pharmacological actions do. This trial is a big part of why the butterbur allergy story is taken seriously despite its narrowness.

The Scottish Challenge Studies

A separate group in Dundee ran a series of smaller, more mechanistic studies, and reporting them honestly means reporting a mixed picture.

• Lee and colleagues, 2003 (Clinical and Experimental Allergy): butterbur attenuated nasal responsiveness to an inhaled adenosine monophosphate challenge in seasonal allergic rhinitis. AMP challenge is an objective provocation test rather than a symptom diary — harder to influence by expectation. A supportive, mechanistically interesting result.
• Gray and colleagues, 2004 (Annals of Allergy, Asthma & Immunology): a placebo-controlled evaluation of butterbur in intermittent allergic rhinitis. A small crossover study rather than a large parallel trial.
• Lee and colleagues, 2004 (Clinical and Experimental Allergy): butterbur and fexofenadine compared on objective and subjective outcomes in perennial allergic rhinitis — the year-round, dust-mite-driven form rather than seasonal pollen allergy.
• Jackson, Lee and Lipworth, 2004 (Annals of Allergy, Asthma & Immunology): looked at butterbur’s effect on skin responses to histamine and to allergen, a different readout entirely from nasal symptoms.

Two honest observations about this group of studies. First, they are small — crossover designs with a few dozen participants, powered to detect physiological signals rather than to establish clinical benefit. Second, they are the closest thing in this literature to independent work, since they came from an academic respiratory pharmacology unit rather than the manufacturer’s trial programme. That independence is worth something even when the individual results are modest or mixed. The overall pattern from Dundee is of a measurable but not dramatic effect on objective nasal measures, which is roughly what you would expect from a leukotriene-directed agent.

What Independent Reviewers Concluded

Guo, Pittler and Ernst reviewed the herbal-medicine evidence for allergic rhinitis in the Annals of Allergy, Asthma & Immunology in 2007 — a group with a long record of being unsparing about weak botanical claims. Butterbur emerged as among the better-supported herbal options for allergic rhinitis, while the review was clear that the evidence base overall was limited and that the encouraging results rested on a small number of trials of a single preparation.

That is a fair place to land. Butterbur is not in the same category as most herbal allergy remedies, which have essentially nothing. It is also not in the same category as intranasal corticosteroids, which have dozens of trials, tens of thousands of participants, and multiple independent manufacturers.

Asthma: The Weakest Claim

You will occasionally see butterbur recommended for asthma. The evidence for that is thin enough to state in one paragraph.

Danesch published an open trial of butterbur root extract in asthma in Alternative Medicine Review in 2004. Participants knew what they were taking, and there was no control group. Asthma symptoms and peak-flow readings fluctuate with season, adherence, infection and attention — all of which improve in anyone enrolled in a study and asked to keep a diary. An uncontrolled asthma study cannot separate a drug effect from any of that.

Asthma is also a condition where getting it wrong is dangerous. Under-treated airway inflammation kills people, and substituting an unproven botanical for inhaled corticosteroids is one of the classic routes to a preventable asthma death. Do not use butterbur in place of asthma medication. If your asthma is not controlled, that is a conversation with a doctor, not a supplement shelf.

Leukotrienes: Why This Might Work

The pharmacological case for butterbur in allergy is more coherent than the case in migraine.

Laboratory work by Thomet and colleagues found that a butterbur extract suppressed leukotriene production in human inflammatory cells, and that petasin accounted for a large share of that activity. Leukotrienes are exactly the mediators responsible for the nasal blockage and swelling that antihistamines handle badly. A follow-up review by the same group summarised the preclinical and clinical picture for petasins in allergic disease.

So the chain of reasoning is: butterbur contains petasin → petasin inhibits leukotriene synthesis → leukotrienes cause nasal congestion → butterbur should reduce nasal congestion. Each link has support, and the clinical trials are broadly consistent with the prediction. That coherence is genuinely reassuring. It is still not proof: nobody has shown that butterbur relieves human hay fever by inhibiting leukotrienes, and all the mechanistic work is cell-culture, not human.

It is worth noting the pharmacological company this puts butterbur in. Montelukast is a leukotriene-receptor antagonist — a well-characterised prescription drug that works on the same pathway, is available cheaply as a generic, and carries its own (neuropsychiatric) warnings. If the leukotriene pathway is what you want to hit, there is a licensed way to do it.

Dose, Season Timing and What to Expect

Again: information, not a recommendation. The safety article should be read first.

Practical realities. Butterbur is short-acting and needs dosing several times a day, which most people manage badly. Its commonest side effects are gastrointestinal — burping with a distinctive and unpleasant taste, mild nausea, stomach upset. It costs considerably more than a generic antihistamine. And the trial evidence covers two weeks, while hay fever season runs for months, so anyone using it across a full season is extrapolating well beyond the data — which is exactly the situation the liver-safety concern makes uncomfortable.

Set against the standard toolkit: intranasal corticosteroids are the most effective single treatment for allergic rhinitis and act on congestion better than anything else here; saline rinses are free, harmless and genuinely useful; second-generation antihistamines are cheap, once-daily and mostly non-sedating; and montelukast targets the same leukotriene pathway butterbur aims at, with a prescriber supervising. Butterbur is not the obvious first move against that list.

The Ragweed Problem

This deserves its own section, because it is a specific hazard that applies to this indication more than any other.

Butterbur belongs to the Asteraceae — the daisy or composite family. So do ragweed, chrysanthemum, marigold, daisy, chamomile, echinacea, arnica, dandelion and feverfew. Members of this family share allergenic proteins and, in contact allergy, share sesquiterpene lactone allergens; reviews of allergy to Asteraceae medicinal plants describe exactly this pattern of cross-sensitisation.

The irony is sharp. Ragweed is one of the leading causes of seasonal allergic rhinitis in North America. Someone with bad autumn hay fever is therefore disproportionately likely to be ragweed-sensitised — and is being offered a remedy from ragweed’s own botanical family. It is entirely possible to take a butterbur product for hay fever and have an allergic reaction to it.

If you know you react to ragweed, chrysanthemums, marigolds, daisies, chamomile or echinacea, treat butterbur as high-risk. Reactions can range from worsened rhinitis and itching to rash to, rarely, more serious allergic responses. A pharmacological detail worth knowing: the petasins are sesquiterpene esters, chemically distinct from the sesquiterpene lactones that cause classic Compositae contact dermatitis — but a plant extract contains far more than its marker compound, so this is not a reason to relax.

Cautions and the Safety Ceiling

Everything in this article sits underneath the ceiling described in Pyrrolizidine Alkaloids and Liver Safety. The short version, allergy-specific:

• Only a certified PA-free standardised extract. Butterbur leaf and root both carry hepatotoxic pyrrolizidine alkaloids. There is no safe home preparation. A butterbur tea for hay fever is a genuinely bad idea.
• Never in pregnancy or breastfeeding. Hay fever in pregnancy is common and there are well-characterised safe options — saline, and specific antihistamines and nasal steroids your obstetric team can name. Butterbur is not among them.
• Not for children. Childhood hay fever is very common and very treatable by conventional means; there is no case for exposing a child to this risk.
• Not with liver disease, regular alcohol, or alongside other liver-loading medicines — and not stacked with other pyrrolizidine-alkaloid herbs such as comfrey, coltsfoot or borage.
• Asteraceae allergy — see above.
• Time-limit it. The trials ran two weeks. A whole season of daily butterbur is not something the evidence covers.
• Never as a substitute for asthma medication.
• Stop immediately for jaundice, dark urine, pale stools, persistent nausea, right-sided abdominal pain or unexplained fatigue.

The Honest Verdict

• The evidence is real and better than most herbal allergy claims. A 330-person placebo- and fexofenadine-controlled trial, a 186-person dose-response study, and objective nasal-challenge work from an independent academic group is a genuine body of evidence.
• “As good as an antihistamine” is overstated. The cetirizine trial had 125 people and no placebo arm; that design cannot establish equivalence. The defensible statement is that butterbur beat placebo and performed comparably to an antihistamine in short trials that were not built to prove equivalence.
• The mechanism fits — leukotriene inhibition, targeting congestion, the symptom antihistamines handle worst — but the mechanistic work is all cell-culture.
• The literature is narrow and short. One product, largely one investigator, two-week trials, for a condition that lasts months.
• Asthma is not supported by anything better than an uncontrolled open trial.
• The safety ceiling applies in full, and the Asteraceae cross-reactivity issue bites hardest in exactly the people seeking hay-fever relief.
• Therefore: nasal steroids, saline rinses and non-sedating antihistamines first. Butterbur is a considered option for someone who has tried those, tolerates them poorly, and can obtain a certified PA-free standardised product — used for a defined period, with a clinician informed.

Back to Table of Contents

Key Research Papers

Every identifier below was verified live against the NCBI PubMed database — title, first author, journal and year all had to match. Study type and size are stated where known, and the limitations are stated with the results.

The randomised trials

1. Schapowal A. Treating intermittent allergic rhinitis: a prospective, randomized, placebo and antihistamine-controlled study of butterbur extract Ze 339. Phytotherapy Research. 2005;19(6):530–537. Human randomised trial, 330 participants, two weeks; butterbur and fexofenadine both improved symptoms versus placebo and were comparable to each other. The best single piece of evidence butterbur has in allergy.
2. Schapowal A. Butterbur Ze339 for the treatment of intermittent allergic rhinitis: dose-dependent efficacy in a prospective, randomized, double-blind, placebo-controlled study. Archives of Otolaryngology–Head & Neck Surgery. 2004;130(12):1381–1386. Human randomised trial, 186 participants; dose-dependent benefit over placebo — the dose-response pattern is the most persuasive feature of this literature.
3. Schapowal A. Randomised controlled trial of butterbur and cetirizine for treating seasonal allergic rhinitis. BMJ. 2002;324(7330):144–146. Human randomised trial, 125 participants, two weeks; comparable symptom relief to cetirizine with less sedation. No placebo arm, and far too small to establish equivalence.

Objective and mechanistic studies from an independent group

1. Lee DK, Carstairs IJ, Haggart K, Jackson CM, Currie GP, Lipworth BJ. Butterbur, a herbal remedy, attenuates adenosine monophosphate induced nasal responsiveness in seasonal allergic rhinitis. Clinical and Experimental Allergy. 2003;33(7):882–886. Small human challenge study using an objective provocation test rather than symptom diaries.
2. Lee DK, Gray RD, Robb FM, Fujihara S, Lipworth BJ. A placebo-controlled evaluation of butterbur and fexofenadine on objective and subjective outcomes in perennial allergic rhinitis. Clinical and Experimental Allergy. 2004;34(4):646–649. Small crossover study in year-round, not seasonal, allergic rhinitis.
3. Gray RD, Haggart K, Lee DK, Cull S, Lipworth BJ. Effects of butterbur treatment in intermittent allergic rhinitis: a placebo-controlled evaluation. Annals of Allergy, Asthma & Immunology. 2004;93(1):56–60. Small placebo-controlled crossover evaluation.
4. Jackson CM, Lee DK, Lipworth BJ. The effects of butterbur on the histamine and allergen cutaneous response. Annals of Allergy, Asthma & Immunology. 2004;92(2):250–254. Skin-response study — a different readout from nasal symptoms, and not a clinical efficacy trial.

Independent review, and the asthma question

1. Guo R, Pittler MH, Ernst E. Herbal medicines for the treatment of allergic rhinitis: a systematic review. Annals of Allergy, Asthma & Immunology. 2007;99(6):483–495. Independent systematic review; butterbur among the better-supported herbal options, on a limited evidence base tied to one preparation.
2. Danesch UC. Petasites hybridus (butterbur root) extract in the treatment of asthma — an open trial. Alternative Medicine Review. 2004;9(1):54–62. Open, uncontrolled trial. Cannot separate treatment effect from natural fluctuation, and asthma is not a condition in which to accept weak evidence.

Pharmacology of the petasins

1. Thomet OA, Wiesmann UN, Schapowal A, Bizer C, Simon HU. Role of petasin in the potential anti-inflammatory activity of a plant extract of Petasites hybridus. Biochemical Pharmacology. 2001;61(8):1041–1047. Cell-culture study identifying petasin as the principal driver of leukotriene suppression.
2. Thomet OA, Simon HU. Petasins in the treatment of allergic diseases: results of preclinical and clinical studies. International Archives of Allergy and Immunology. 2002;129(2):108–112. Review linking the laboratory pharmacology to the clinical results.

Asteraceae allergy and cross-reactivity

1. Ključevšek T, Kreft S. Allergic potential of medicinal plants from the Asteraceae family. Health Science Reports. 2025;8(2):e70398. Review of allergy risk across the daisy family — the family butterbur, ragweed, chamomile and feverfew all belong to.
2. Denisow-Pietrzyk M, Pietrzyk Ł, Denisow B. Asteraceae species as potential environmental factors of allergy. Environmental Science and Pollution Research International. 2019;26(7):6290–6300.

Live PubMed Searches

1. Ze 339 allergic rhinitis
2. Butterbur and hay fever
3. Petasites hybridus rhinitis
4. Petasin and leukotriene inhibition
5. Leukotrienes and nasal congestion
6. Intranasal corticosteroids for rhinitis
7. Ragweed and Asteraceae cross-reactivity
8. Herbal medicines for allergic rhinitis

Connections

• Butterbur Benefits — hub
• Pyrrolizidine Alkaloids and Liver Safety
• Choosing a PA-Free Product
• Migraine Prevention
• Butterbur
• Stinging Nettle — another hay-fever herb
• Quercetin
• Chamomile — another Asteraceae member
• Echinacea — another Asteraceae member
• Pain & Allergy
• Histamine, Mast Cells & Allergy — interactive animation
• Comfrey
• All Herbs

Back to Table of Contents