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For horses · Jan 28, 2015

Comfrey contains real liver toxins, that’s not industry scaremongering

Comfrey (Symphytum officinale) holds compounds that can harm the liver with repeated exposure, and the evidence for that is solid enough to take seriously.

Brown tabby cat beside a comfrey plant in flower — pyrrolizidine alkaloids make comfrey toxic internally

By Beryl Shuttleworth, BSc Hons Biochem

Last reviewed: 2026-06-12

Comfrey (Symphytum officinale) is genuinely risky taken internally. It contains compounds called pyrrolizidine alkaloids, which the liver converts into reactive substances that damage liver cells, block blood vessels within the liver, and can trigger liver cancer through DNA damage. The root contains higher alkaloid levels than the leaves, and whole-plant preparations appear more harmful than any single alkaloid in isolation. Used on the skin, the risk is lower but not zero, these alkaloids can be absorbed, which is why regulators cap daily dermal exposure at 100 µg. PA-depleted topical extracts, the kind used in modern clinical formulations, have shown genuine efficacy and a much better safety profile in randomised controlled trials.

Comfrey is only dangerous if you eat it, topical use is safe

It’s an easy assumption to make. The most alarming comfrey stories involve people drinking comfrey tea or taking capsules, and regulatory bodies like the FDA and EMA have specifically gone after oral products. The EMA even restricts comfrey root to external use only. If the regulators are comfortable with putting it on the skin, surely the skin keeps it out?

The trouble is, it doesn’t, not reliably.

Pyrrolizidine alkaloids (PAs) can cross the skin and enter the bloodstream. We know this because health authorities have set a ceiling of 100 µg of PAs per day for topical products specifically to limit how much gets absorbed into the body [9]. The EMA’s more permissive stance on topical comfrey comes with strict conditions: no more than 0.35 µg of PAs reaching the skin per day, and use limited to short periods of up to 10 days [7]. That’s not a green light, it’s a carefully managed risk threshold.

And the reason those limits matter comes down to what happens once PAs reach the liver. Enzymes there (part of the cytochrome P450 family) convert PAs into reactive compounds that can damage liver cells, block blood vessels within the liver, and interact with DNA in ways that can trigger mutations [1, 6]. The liver doesn’t know or care whether the PAs arrived via the mouth or through the skin.

There’s another wrinkle worth knowing about. A crude comfrey extract has been shown to be more toxic than its individual alkaloids tested separately, the mixture appears to be more harmful than the sum of its parts [5]. This matters because many “low-PA” product claims are based on testing a single isolated alkaloid, which is likely to paint a rosier picture than the whole plant deserves.

The genuinely reassuring option is a PA-depleted or PA-free extract. These have been tested in proper clinical trials for muscle and joint complaints and shown to work well at PA concentrations below 0.35 ppm [11]. But that’s a very different thing from saying standard comfrey preparations are fine on the skin. Most products don’t state their PA content on the label [8], which means there’s really no way of knowing whether you’re within any safe limit at all.

How pyrrolizidine alkaloids damage the liver

Comfrey (*Symphytum officinale*) contains compounds called pyrrolizidine alkaloids (PAs), the main ones being intermedine and lycopsamine. On their own, these molecules don’t cause immediate harm. The trouble starts when the liver attempts to break them down.

The liver uses enzymes called hepatic cytochrome P450s to process the PAs. In doing so, it converts them into highly reactive breakdown products known as pyrrolic metabolites. These metabolites attack the cells lining the liver’s tiny blood vessels, causing a condition called sinusoidal obstruction syndrome, essentially a blockage of blood flow through the liver. At the same time, intermedine triggers cell death in liver tissue by generating damaging molecules called reactive oxygen species and disrupting how the cells produce energy (mitochondrial dysfunction). The more exposure, the worse the damage.

There’s another layer of harm too. The pyrrolic metabolites bind directly to DNA, forming what are called pyrrole-DNA adducts. These cause genetic mutations and can set the stage for liver cancer, not just liver inflammation.

Whole comfrey appears to be more dangerous than any single alkaloid in isolation. When a reduced whole-plant extract was tested against purified intermedine or lycopsamine individually, the whole extract was more toxic, suggesting the alkaloids work together in a way that’s worse than the sum of their parts. This matters because safety assessments based on individual alkaloids can seriously underestimate the risk of the whole plant.

The root reliably contains higher PA levels than the leaves, anywhere from 0.013% to 1.2% by weight, depending on where the plant was grown and when it was harvested. Some products on the market exceed the recommended daily exposure limits set by the EMA.

Even used on the skin, there is some risk. PAs can be absorbed through intact skin, though absorption is relatively slow. Regulators cap topical PA exposure at 100 μg per day. The EMA limits comfrey root preparations to external use only, for no longer than 10 days at a time, with a PA ceiling of 0.35 μg/day, a figure that traces back to a tolerable daily intake of 0.1 μg/kg body weight/day, set 100-fold below the level at which no adverse effects were observed in long-term animal studies.

It’s worth being clear that comfrey also contains genuinely useful compounds, allantoin, rosmarinic acid, and polysaccharides that have real anti-inflammatory and tissue-repair activity, working through pathways like NF-κB and MAPK inhibition. This is exactly why PA-depleted extracts have been developed for topical clinical use. The toxicity problem is real, but so is the therapeutic potential, and separating the two is the whole point.

How to use comfrey safely, what the evidence actually permits

Topical use only

The only way any regulatory body currently sanctions comfrey use is as an external application, something you put on the skin, not something you swallow. The EMA allows comfrey root preparations to be used topically for short periods, up to 10 days, and sets a daily limit of no more than 0.35 μg of pyrrolizidine alkaloids (PAs) from the product. For dermal exposure more broadly, a ceiling of 100 μg of PAs per day has been established to keep systemic absorption through intact skin within safe bounds.

If you are choosing a topical comfrey product, look specifically for one made with a PA-depleted or PA-free extract. The clinical trials that have shown real results for painful muscles and joints, acute back pain, osteoarthritis, and bruising injuries used root extracts with PA content below 0.35 ppm, not whole-plant preparations.

What to cheque on the label

PA content in comfrey varies enormously. Commercial root preparations have been measured anywhere between 0.013% and 1.2% PAs by weight, depending on which part of the plant was used, where it was grown, and when it was harvested, and some products on the market have been found to exceed EMA daily limits. If a product does not clearly state its PA content, or confirm that a PA-depleted extract was used, you simply cannot know whether it falls within the safe limit.

Duration

The EMA guidance is up to 10 days for topical use. Nothing in the research I have drawn on here supports extended or repeated-course use beyond that window.

Oral use

The U.S. FDA requested voluntary withdrawal of oral comfrey products in 2001. Oral comfrey is now banned or restricted in most countries. There is no dose of oral comfrey that the research here identifies as safe, the liver damage caused by PAs is cumulative, dose-dependent, and irreversible. I would not recommend oral comfrey in any form, for any species.

Contraindications for topical use

Pyrrolizidine alkaloids can be absorbed through intact skin, which is precisely why regulatory limits exist for topical products. Dermal absorption may be low, but it is not zero. On that basis, applying comfrey to broken or damaged skin, where absorption would be higher, is not covered by the safety assessments referenced here and should be avoided.

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Frequently asked questions

Are pyrrolizidine alkaloids in comfrey actually dangerous, or is that overstated?

The danger is real and well-documented. Comfrey (*Symphytum officinale*) contains pyrrolizidine alkaloids that the liver converts into reactive compounds capable of damaging liver cells, blocking blood flow through the liver, and attaching to DNA in ways that can trigger cancer. The damage builds with each exposure and is largely irreversible, so there is no safe level for repeated oral use.

Is comfrey root more toxic than the leaves?

Yes, consistently. Comfrey roots contain higher pyrrolizidine alkaloid levels than leaves, measured at 0.013% to 1.2% by weight, depending on where the plant was grown and when it was harvested. Some commercial root preparations exceed the EMA’s recommended daily alkaloid limits. There is also evidence that crude whole-plant preparations are more toxic than the same quantity of isolated alkaloids, pointing to some kind of additive or combined effect between the different alkaloid forms present.

Is topical comfrey safe because it doesn’t go through the digestive system?

Not automatically. Pyrrolizidine alkaloids can cross intact skin and enter the bloodstream, which is why regulators have set a limit of 100 μg of daily dermal exposure. The EMA restricts comfrey root preparations to external use only, for no more than 10 days at a time, with pyrrolizidine alkaloid content capped at 0.35 μg per day. Most product labels do not state alkaloid content clearly enough for anyone to cheque whether these limits are actually being met.

Are there any comfrey products that are considered safe?

Some are. Topical formulations using pyrrolizidine-depleted or pyrrolizidine-free extracts have performed well in randomised controlled trials for muscle and joint pain, back pain, and osteoarthritis, without the liver safety concerns seen with whole-plant preparations. The critical requirement is confirmed PA depletion below 0.35 ppm, backed by analytical testing, not just a marketing claim. I would not recommend any oral comfrey product, and I would not use a topical product that cannot verify its alkaloid content.

Does comfrey have any genuine therapeutic compounds, or is it all risk?

It does contain genuinely useful things, allantoin, rosmarinic acid, polysaccharides, and lignans that help reduce inflammation and support tissue repair. The difficulty is that these beneficial compounds sit alongside the pyrrolizidine alkaloids in the intact plant. That is precisely why any responsible therapeutic use today is built on PA-depleted extracts, not whole-plant preparations.

Can low-dose or short-term comfrey exposure cause liver damage?

Yes. In rat studies, weekly dosing at 50 mg/kg of comfrey-derived alkaloids for just six weeks produced congestion in liver blood vessels, death of liver cells, damage to the vessel lining, and visible structural changes at the cellular level. Pyrrolizidine alkaloid toxicity is cumulative, each exposure adds to the total load, so a low dose does not mean a safe dose when use is repeated over time.

Sources

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