Pyrrolizidine Alkaloids, Comfrey, and the Boraginaceae Family
By the Seed SistAs
For a couple of decades now there has been much talk and controversy about the herb Comfrey. When we did our clinical training in medical herbalism in the early 2000s, we were taught about the powerful bone knitting properties of comfrey and how this works to increase the rate of renewal in the bone cells. A few years later, reports started coming in about potential causation of liver toxicity with internal preparations, and later still an agreed code amongst the herbal medicine community not to work with comfrey internally any longer; external preparations only. Several years after that we heard of a liver issue in a hospital that was blamed by the medical staff on external use of a coffer preparation. It absolutely turned out not to be the comfrey but an underlying liver disorder, but the hype at the time was such, that comfrey got the blame.
So what’s actually going on and how did this all begin?
Pyrrolizidine Alkaloids (PAs) were first discovered in plants in the 19th century, but their toxic effects were not immediately recognised. Instead, many PA-containing plants have been traditionally used for medicinal purposes in various cultures around the world.
For centuries, herbalists have turned to plants from the Boraginaceae family for their medicinal benefits. Among them, comfrey (Symphytum officinale) stands out as a cornerstone of traditional herbal medicine—used in poultices for wounds, teas for internal healing, and salves for bone repair. But nestled within these healing plants is a potentially toxic secret: pyrrolizidine alkaloids (PAs), naturally occurring compounds that are purported to pose serious health risks.
The Boraginaceae Family: An Overview
The Boraginaceae, or borage family, is a large and diverse group of flowering plants with over 2,000 species distributed worldwide. Well-known members include:
- Comfrey (Symphytum spp.)
- Borage (Borago officinalis)
- Alkanet (Alkanna tinctoria)
- Hound’s Tongue (Cynoglossum officinale)
- Forget-Me-Not (Myosotis spp.)
These plants are often coarse, hairy (can cause irritation when harvested with bare hands), and rich in mucilage, with a long-standing reputation for their emollient and anti-inflammatory properties.
Many herbs of the Boraginaceae family (as well as others such as certain members of the Daisy Family) also contain the PAs, as a chemical defence mechanism evolved to deter herbivores.
Other PA-Containing Members of Boraginaceae
While comfrey gets the spotlight, other plants in the family are also coming under scrutiny:
- Borage: Used as a culinary and medicinal herb; contains less PA than comfrey but still not recommended for long-term internal use.
- Chinese Forget-me-not: Traditionally used as a sedative and for skin complaints; since found to be toxic.
- Alkanet/bugloss and Heliotropium: Often grown ornamentally, but their PA content poses potential risks to livestock and pollinators.
What are Pyrrolizidine Alkaloids?
Pyrrolizidine alkaloids (PAs) are a class of secondary metabolites (meaning they are for secondary purposes in the plant, in this instance, protection rather than directly involved in the growth and reproduction of a plant). These are just one type of compound found in these plants, there are many other beneficial medicinal qualities but these PAs have had arguably the most controversy around them in recent times.
After oral ingestion PAs are absorbed from the gastrointestinal tract. Most of them, around 80%, are excreted in urine, faeces and in pregnant women and animals the milk. Bioactivation occurs mostly in the liver and, for this reason, this organ is the most affected by toxicity. Other organs can be affected, namely the lungs and kidneys. The lung is the second most affected organ by the pyrroles formed after metabolic activation in the liver, since they can travel to the lungs through blood. For PA to be excreted or exert toxicity, as with many xenobiotics, biotransformation (in the liver) must occur (Moiera et al, 2018). There is much information to suggest that concentrated or prolonged ingestion of PA containing herbs can cause issues.
However, a paper in 2016 claims that over one month no traceable amount of toxicity was noted with comfrey ingestion (Seremet et al 2016). The suggestion is that this would need to be repeated to confirm these findings or happen over a longer time period. But this is obviously not ethical to carry out and we don’t agree with animal testing.
What is clear is that PA derived components in the blood in concentrated doses will affect the DNA of cells causing mutations and serious health issues. This does not give a clear picture about the long-term effects; however caution has been implemented across the herbal community showing the power of self-regulation particularly here in the UK.
Health Risks of Pyrrolizidine Alkaloids
- Hepatotoxicity: Once metabolised by the liver, PAs can form toxic pyrroles that damage liver cells, potentially leading to veno-occlusive disease, liver fibrosis, or even cancer. The research is inconclusive around how much for how long, if it’s the whole plant, and whether the toxic versus the beneficial actions weigh each other out. Many of the uses for comfrey involve short term use, such as bone fractures or breaks, stomach ulcers that need a very short stint of powerfully healing, and richly mucilaginous plants even just for a few days. Many studies show that it’s more likely to be a cumulative toxicity rather than something more instantly ‘poisonous’
- Cumulative toxicity: PAs accumulate in the body, and damage may not be apparent until significant injury has occurred. This is the unfortunate thing about comfrey toxicity. If there is damage, it will be a challenge to heal or reverse it because of the mode of damage created by entering the cells and affecting the DNA.
- Teratogenic and carcinogenic potential: PAs can cause developmental anomalies and tumours. PAs are present in ragwort which is pulled up in horse pasture. Generally a horse will not eat ragwort unless access to other forage is scarce. A mare that had consumed ragwort gave birth to a foal that died of liver failure shortly after birth. Comfrey does not have as high concentration of PAs as ragwort and humans have a different constitution than horses, but we can see the PAs in action here in the liver.
There is even research being done into different products for food and medicine that might have been growing with PA containing herbs or honey that has been made from nectar of PA containing plants as a potential source!!!!
How and Why to Use Comfrey
Comfrey, long called “knitbone” or “boneset,” has been a favorite among herbalists for its ability to promote tissue regeneration. Comfrey’s use dates back to classical antiquity, noted by Greek physicians like Dioscorides and Galen. In medieval European herbals, it appears frequently as a remedy for internal bleeding and broken bones. Even Nicholas Culpeper, the 17th-century English herbalist, praised it as “a comfort to inward wounds and bruises.”
Traditionally, the root and leaves were used for:
- Bruises and sprains
- Bone fractures
- Skin inflammation
- Gastric ulcers and coughs
Historically, the plant’s dangers were unknown—or perhaps viewed as worth the risk. The line between medicine and poison was thinner in pre-modern herbalism, with empirical knowledge passed down orally and refined through trial and error.
Regulatory Response to Comfrey
- Internal use of comfrey has been banned or agreed to be restricted in many countries, including the U.S., Canada, U.K., and Germany.
- Topical use is often still permitted in limited doses and timeframes, particularly with PA-free extracts (though these are rare and not always reliably verified).
Modern Herbalism and Risk Assessment
The tension between traditional herbal practice and modern toxicology is particularly sharp with plants like comfrey. Herbalists today face a complex question: how do we honour ancestral knowledge while acknowledging contemporary scientific understanding? Sometimes the potential risks aren’t worth it and modern research is worth watching and listening to as long as it is relevant to the way that herbs will be taken and in the correct form. There is little point taking one isolated compound, giving large doses and then saying it’s toxic. We work with comfrey as an external preparation and find the effects so powerful, along with horseradish and heather.
Best Practices of PAs:
- Avoid internal use of comfrey and other PA-containing herbs
- Label herbs carefully in home apothecaries.
- Educate clients or students about the potential risks of PAs but also weigh up for them the way that research is conducted generally;
- Promote safe alternatives such as calendula, plantain, or marshmallow root for skin and tissue repair.
The story of pyrrolizidine alkaloids and comfrey, and the Boraginaceae family, is a reminder that even the most beloved healing plants can gain a reputation. For those who honour plant medicine—whether as historians, witches, or botanists—it’s vital to blend respect for traditional use with modern awareness of safety.
The knowledge is not lost, but it must be updated, filtered through both tradition and science. In doing so, we preserve not only the past but the future of herbal wisdom.
References for Pyrrolizidine Alkaloids and Comfrey:
Rom J Morphol Embryol. 2016;57(3):1017-1023. Oral toxicity study of certain plant extracts containing pyrrolizidine alkaloids. Oana Cristina Şeremet, Florica Bărbuceanu, Floriana Elvira Ionică, Denisa Marilena Margină, Claudia Maria GuŢu, Octavian Tudorel Olaru, Mihaela Ilie, Veaceslav Gonciar, Simona Negreş, Cornel ChiriŢă
Int J Mol Sci. 2018 Jun 5;19(6):1668. Pyrrolizidine Alkaloids: Chemistry, Pharmacology, Toxicology and Food Safety. Rute Moreira, David M Pereira, Patrícia Valentão, Paula B Andrade
PMCID: PMC6032134 PMID: 29874826
These blog articles are herbal education resources, produced by the Seed Sistas. Gain insights and join us in the evolution of healthcare, please do leave a comment or question. Wellbeing empowerment for all…
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