Pyrrolizidine Alkaloids: Comfrey, Coltsfoot, Borage and Liver Veno-Occlusive Disease
Pyrrolizidine alkaloids in comfrey, coltsfoot, borage and butterbur can injure the liver. See what the EU committee and other sources say, what PA-free means and who is most at risk.
Content last updated . This page has not been medically reviewed.
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Safety first. Pyrrolizidine alkaloids (PAs) are plant compounds that can damage the liver. NCCIH says PAs can damage the liver and lungs and may cause cancer. [1] The EU herbal committee (HMPC, 2014) says liver toxicity from the toxic, unsaturated PAs is established. [2] It also says symptoms may take several days or months to appear. [2] Call a clinician about belly swelling or other liver warning signs after a PA plant (see the liver warning signs link below). For a swallowed plant or product, Poison Help is 1-800-222-1222; for collapse or severe symptoms call 911.
What PAs are and which plants carry them
The HMPC statement says PAs occur in more than 6,000 plants, mainly in the Boraginaceae, Asteraceae (certain tribes) and Fabaceae families, and that about half of more than 350 known PAs are assumed to be liver-toxic. [2] Plants discussed here:- Comfrey, Symphytum officinale L. (Boraginaceae). [3]
- Coltsfoot, Tussilago farfara L. (Asteraceae). [4]
- Borage, Borago officinalis L. (Boraginaceae). [5]
- Butterbur, Petasites hybridus (L.) G.Gaertn., B.Mey. & Scherb. (Asteraceae). [6]
The HMPC statement lists extracts of coltsfoot, comfrey and a Petasites species among plants with animal cancer evidence, while saying the International Agency for Research on Cancer found the compounds not classifiable as carcinogenic for humans. [2]
Traditional use
This is tradition, not proof. LactMed says comfrey has been used on the skin for pain after episiotomy and for cracked nipples, and that scientific evidence for those uses is minimal. [7] A 1976 paper calls coltsfoot widely used as a herbal remedy. [8] NCCIH says butterbur has been used for health purposes for many centuries. [1] The HMPC notes that leaves of borage and comfrey have been recommended as salads, which is a food use, not a remedy. [2]What the sources found
| Plant or product | What the source found | Strength of evidence |
|---|---|---|
| Comfrey by mouth | Case reports from 1987 and 1989 are titled "veno-occlusive disease of the liver secondary to ingestion of comfrey" and "comfrey herb tea-induced hepatic veno-occlusive disease". [9][10] The HMPC says the lowest intake linked to this disease in a person came from self-medication with a comfrey preparation. [2] | Evidence of harm (case reports) |
| Coltsfoot | An 18-month-old boy developed this liver disease after a herbal tea mixture; the leaf the parents gathered was a look-alike, not coltsfoot, and he recovered within 2 months. [11] In rats, a coltsfoot flower diet produced liver tumors, attributed mostly to the PA senkirkine. [8] | Evidence of harm (case report); preclinical (rats) |
| Borage leaf | Borage is listed among PA-producing plants recommended as salad leaves. [2] | Documented hazard; human cases not described in the sources we read |
| Borage seed oil | A 2018 risk assessment expected no health risk from supplements made from oil-based preparations of PA-producing plants that were described as free of PAs. [12] One commercial borage seed oil sample tested below 200 parts per trillion. [13] | Low expected risk for PA-free oil; one product tested |
| Butterbur | PA-free products seem safe in studies of up to 16 weeks, but rare liver injury was reported with products labeled PA-free. [1] The American Academy of Neurology stopped recommending it in 2015 over safety. [1] | Promising but limited; safety concerns |
| Tusanqi products | A systematic review of 106 articles calls Tusanqi a major cause of this liver disease in China; belly swelling (ascites) was most common. [14] | Evidence of harm (case series) |
PA liver injury is described as long overlooked, and treatment is largely supportive. [15] It can be misread as another cause, such as alcohol. [2]
Creams and skin
In a laboratory model of human skin, three PAs added to one comfrey root formulation penetrated little. [16] That does not show a product is safe. NCCIH warns PAs could be absorbed through cuts or scrapes. [1] See comfrey and butterbur.Look-alike plants
The infant case above shows how a similar-looking plant can replace the one intended. [11] Its authors say plant material should be checked by trained experts. [11] Do not rely on a photo or app; ask Poison Help, a local botanist or an extension service, and read plant and mushroom poisoning.Related: liver warning signs, how herbs and medicines interact, quality testing. Tell clinicians about every herb. [17]
Frequently asked questions
Is comfrey safe to take?
No. LactMed says the pyrrolizidine alkaloids in comfrey can cause severe liver damage, liver cancer and death, and that oral comfrey products are banned for sale in the US. [7]
Is borage oil the same as borage leaf?
No. The leaf is a PA-producing plant; supplements from oil-based preparations described as PA-free were not expected to carry a risk in a 2018 assessment. [2][12] Product-specific testing is not described in the sources we read.
What does PA-free mean?
NCCIH says only butterbur products processed to remove PAs and labeled or certified PA-free should be considered. [1] It also says rare liver injury has been reported with products labeled PA-free. [1]
Are coltsfoot teas or lozenges safe?
Proper evidence not found for a safe amount in the sources we read. They describe harm in an infant and tumors in rats. [11][8]
What should I do if I think I was exposed?
Call Poison Help (1-800-222-1222) or a clinician and tell them the product. Ask the prescriber or pharmacist before changing any medicine. Report through side effects and reporting.
More details: evidence, limits and cautions
The details behind this page: cautions, limits of the evidence and where sources disagree. Open any note to read it.
What regulators say
- EU (HMPC, 24 November 2014): dose and effect remain unclear and people differ widely in susceptibility; it described these poisonings as an "iceberg disease". [2] For herbal medicines it judged a daily intake of 0.35 micrograms of toxic PAs for up to 14 days might be acceptable. [2] That is a regulatory risk figure for manufacturers, not advice for readers.
- US: the HMPC statement says the FDA advised supplement makers in 2001 to remove comfrey and other PA-containing products. [2] LactMed says the FDA banned the sale of oral comfrey products. [7]
- Food: a 2018 assessment found herbal teas and teas are the main common-food source of PA exposure; short-term intake was judged unlikely to cause acute damage, but high long-term intake raised concern. [12]
Pregnancy, breastfeeding and children
References
- NCCIH, Butterbur (US NIH). Read 2026-10-23.
- EMA/HMPC, Public statement on the use of herbal medicinal products containing toxic, unsaturated pyrrolizidine alkaloids (PAs), final, adopted 24 November 2014 (EMA/HMPC/893108/2011). Read 2026-10-23.
- GBIF Backbone Taxonomy, Symphytum officinale match record. Read 2026-10-23.
- GBIF Backbone Taxonomy, Tussilago farfara match record. Read 2026-10-23.
- GBIF Backbone Taxonomy, Borago officinalis match record. Read 2026-10-23.
- GBIF Backbone Taxonomy, Petasites hybridus match record. Read 2026-10-23.
- LactMed (US NLM), Comfrey. Read 2026-10-23.
- Carcinogenic activity of coltsfoot, Tussilago farfara L. Gan 1976. Read 2026-10-23.
- Veno-occlusive disease of the liver secondary to ingestion of comfrey. British Medical Journal 1987 (title and citation record). Read 2026-10-23.
- Comfrey herb tea-induced hepatic veno-occlusive disease. American Journal of Medicine 1989 (title and citation record). Read 2026-10-23.
- Reversible hepatic veno-occlusive disease in an infant after consumption of pyrrolizidine-containing herbal tea. European Journal of Pediatrics 1995. Read 2026-10-23.
- Risk assessment of pyrrolizidine alkaloids in food of plant and animal origin. Food and Chemical Toxicology 2018. Read 2026-10-23.
- Evaluation of pyrrolizidine alkaloids in Borago officinalis seed oil by mass spectrometry. Journal of Mass Spectrometry 2013. Read 2026-10-23.
- Tusanqi-related sinusoidal obstruction syndrome in China: a systematic review. Medicine 2015. Read 2026-10-23.
- Hepatic veno-occlusive disease associated with toxicity of pyrrolizidine alkaloids in herbal preparations. Netherlands Journal of Medicine 2010. Read 2026-10-23.
- Percutaneous absorption of retronecine-type pyrrolizidine alkaloids through human skin, in vitro. Planta Medica 2022. Read 2026-10-23.
- NCCIH, Using Dietary Supplements Wisely (US NIH). Read 2026-10-23.