Comfrey (Symphytum officinale L.)
1. Identity, Taxonomy, and Natural Source
Common comfrey (Symphytum officinale) is a perennial herb belonging to the family Boraginaceae, which is native to Europe and Asia, but is now found worldwide. It is native to Europe, growing in damp, grassy places, is found throughout Ireland and Britain on river banks and ditches, and occurs in North America as an introduced species.
Comfrey belongs to the plant family Boraginaceae and there are at least five species referred to as comfrey, including Symphytum officinale L. (the major comfrey species), Symphytum asperum Lepech, Symphytum × uplandicum Nyman, Symphytum tuberosum L., and Symphytum caucasicum Bieb.
Along with thirty-four other species of Symphytum, it is known as comfrey, from the Latin confervere meaning "to heal" or literally "to boil together," referring to uses in ancient traditional medicine. The Greek term symphyton (symphytum in Latin) is derived from symphyo, meaning "I grow together." Solidago, derived from solido ("I make firm"), was also a synonym. The Latin consolida, frequently found in historical papers, means "the one who makes firm."
To differentiate it from other members of the genus Symphytum, this species is known as common comfrey or true comfrey. Other English names include boneset, knitbone, consound, and slippery-root. It is also known by folk names including black wort, bruise wort, and knitback.
Plant Morphology and Parts Used
Comfrey produces large, lance-shaped leaves covered in coarse hairs, and bell-shaped flowers ranging from purple to white. The principal medicinal parts used are the root (radix) and the leaf. The species name officinale indicates its historical inclusion in official pharmacopoeias, underscoring centuries of medicinal recognition.
Common Forms and Preparations
Comfrey is available in several preparation forms. Topical products include ointments, creams, and gels made from root or leaf extracts, as well as poultices made from fresh or dried plant material. Historically, internal preparations included teas (leaf or root decoctions), tinctures, and tablets. Root preparations are utilized for the external treatment of joint complaints, painful muscle, bone fractures, distortions, and haematomas. Nowadays, medicinal products from comfrey root that are commercialized on the European market contain only extracts from pyrrolizidine-depleted plant material or obtained from special cultivars that do not synthesize pyrrolizidine alkaloids.
2. Traditional and Historical Use
Comfrey has been used both internally and externally as an herbal medicine for more than 2,000 years in many countries. The Greeks and Romans commonly used comfrey to stop heavy bleeding, treat bronchial problems, and heal wounds and broken bones. Poultices were made for external wounds and tea was consumed for internal ailments.
Anglo-Saxon herbalists recorded comfrey's use in treating fractures, earning it the enduring nickname "knitbone." Historical texts from Dioscorides (40–90 CE) through Hildegard von Bingen (1098–1179) document comfrey's reputation for "knitting together" damaged tissues. Nicholas Culpeper (1616–54) mentioned the herb in The English Physitian.
Over centuries, comfrey was cultivated in Asia, and in Europe including the United Kingdom, as a vegetable and herbal medicine. Its early common names, knitbone or boneset, reflect its historical use by poultices of leaves and roots to treat sprains, bruises, or bone injuries.
Historical standard publications listed external use as indicated for periosteum problems, bone fractures, promotion of callus formation, neuralgia after fractures, strains, contusions, tenosynovitis, inflammation of a muscle, haematoma, thrombosis, arthritis, wounds that heal badly, and periodontosis. Internal use was directed for gastritis, peptic ulcers, cough remedies, and use in cases of rheumatism, pleurisy, bronchitis, diarrhoea, and tumours.
Traditional European preparation methods included fresh poultices for acute injuries, infused oils for massage, and decoctions applied as compresses.
3. Key Constituents and Active Compounds
From a phytochemical point of view, comfrey roots display polysaccharides (mucilage, up to 30%), purine derivatives (allantoin, 0.6–4.7%), phenolic acids (caffeic acid oligomers, 0.9–4.8%), pyrrolizidine alkaloids (PAs, 0.01–1.2%), triterpene saponins, amino acids, and glycopeptides.
The constituents of comfrey root include 0.6–4.7% allantoin; abundant mucilage polysaccharides (about 29%) composed of fructose and glucose units; phenolic acids such as rosmarinic acid (up to 0.2%), chlorogenic acid (0.012%), as well as caffeic acid (0.004%) and α-hydroxy caffeic acid; glycopeptides and amino acids; and triterpene saponins in the form of monodesmosidic and bidesmosidic glycosides based on the aglycones hederagenin, oleanolic acid, and lithospermic acid.
Comfrey contains as many as 14 pyrrolizidine alkaloids (PA), including 7-acetylintermedine, 7-acetyllycopsamine, echimidine, intermedine, lasiocarpine, lycopsamine, myoscorpine, symlandine, symphytine, and symviridine.
Rosmarinic acid has been identified as the main phenolic constituent (7.55 mg/g extract). Moreover, trimers and tetramers of caffeic acid (isomers of salvianolic acid A, B, and C) have been identified and quantified in comfrey root.
Allantoin
Many members belonging to the borage family, including S. officinale, contain the chemical constituent allantoin, which promotes healing. Comfrey contains about 0.8% allantoin in the root and 0.4% in the leaf preparation. Allantoin might enhance its immunomodulatory and wound healing properties.
Rosmarinic Acid and Phenolic Acids
Rosmarinic acid has been shown to possess anti-inflammatory activity in various test systems. It inhibits the formation of malondialdehyde in human platelets, prostaglandin synthesis, and carrageenan- and gelatine-induced erythrocyte aggregation. Caffeic acid oligomers (e.g., rosmarinic acid, globoidnan A, globoidnan B, rabdosiin) can potentiate the antioxidant and anti-inflammatory efficacy of comfrey extracts.
Mucilage Polysaccharides
Polysaccharides contribute to the immunomodulatory, antioxidant, anticancer, hypoglycemic, and hypolipidemic effects of comfrey. These large carbohydrate molecules form a soothing, protective coating on mucous membranes and skin, historically supporting its use as a demulcent.
Pyrrolizidine Alkaloids (PAs)
PAs (e.g., symphytine, lycopsamine, acetyllycopsamine, intermedine, acetylintermedine, etc.) are generally linked to toxicological issues of comfrey. The pyrrolizidine alkaloids contained in comfrey include intermedine, lycopsamine, symphytine, and echimidine, which are metabolized by the cytochrome P450 enzymes into highly toxic pyrrole metabolites which have alkylating properties that can damage hepatic endothelial cells and can cause sinusoidal obstruction.
4. Mechanisms of Action
The therapeutic properties of comfrey are based on its anti-inflammatory and analgesic effects. Comfrey also stimulates granulation and tissue regeneration, and supports callus formation. However, the key activity-determining constituents of comfrey extracts and their molecular mechanisms of action have not been completely elucidated. Allantoin and rosmarinic acid are probably of central importance to its pharmacodynamic effects.
Preclinical studies suggest allantoin and rosmarinic acid compounds in comfrey may be responsible for cell proliferation and anti-inflammatory effects. Comfrey was also shown to stimulate granulation and tissue regeneration, and support callus formation.
Comfrey root is rich in bioactive compounds, including allantoin, salvianolic acid, and rosmarinic acid, which are known for their great free radical scavenging activity, and the high antioxidant activity of the extract may be mainly due to these compounds.
With respect to pyrrolizidine alkaloid toxicity, the available evidence suggests that the active metabolites of PA in comfrey interact with DNA in liver endothelial cells and hepatocytes, resulting in DNA damage, mutation induction, and cancer development. The mechanisms underlying comfrey-induced genotoxicity and carcinogenicity are still not fully understood.
5. Scientific Evidence by Area of Use
All clinical evidence described below pertains exclusively to topical preparations. No clinical evidence supports internal use as safe, and internal use carries substantial documented toxicity risks (see Section 7).
5.1 Wound Healing
A topically applied preparation containing 10% active ingredient from the aerial parts of comfrey (Symphytum × uplandicum Nyman, Traumaplant®) was examined for wound-healing effects in a randomized, double-blind clinical trial that included 278 patients with fresh abrasions. After 2 to 3 days, a significantly and clinically relevantly faster initial reduction in wound size of 49 ± 19% versus 29 ± 13% per day in favour of verum was found (p < 5 × 10−21).
Macroscopic evaluation and histological analysis of skin defects 14 days after the intervention showed faster healing and complete healing in the skin excisions treated with oil-in-water cream with 20% extract of comfrey as the active ingredient (animal study). This latter result is from a rat model and cannot be directly extrapolated to humans.
A 2024 review suggests topical preparations of comfrey may have positive effects on skin wounds by encouraging cell growth and regeneration. This is because the antioxidant effects of comfrey extracts may contribute to its wound-healing potential. However, more research is needed to confirm its effectiveness and safety.
5.2 Acute Back Pain (Myalgia)
A double-blind, placebo-controlled, multicentre, randomized clinical trial with parallel group design was conducted over a period of 5 days. One hundred and twenty patients with acute upper or lower back pain were treated three times a day, 4 g per application.
A double-blind, reference-controlled, randomized, multicentre trial included 215 patients with pain in the lower and upper back. The primary efficacy parameter was pain in motion, assessed with the aid of a visual analogue scale. Secondary efficacy parameters included pain at rest, pain on palpation, and functional capacity.
Overall, randomized controlled trials demonstrate that topical S. officinale preparations significantly outperform placebo in acute back pain, knee osteoarthritis, ankle sprains, and myalgia, while showing non-inferiority to diclofenac and an excellent safety profile.
5.3 Ankle Sprains and Distortions
In a double-blind, multicenter, randomized, placebo-controlled, group comparison study on patients suffering from unilateral acute ankle sprains (n = 142, mean age 31.8 years, 78.9% male), the percutaneous efficacy of an ointment of comfrey extract (Kytta-Salbe f, four treatments per day for 8 days) was confirmed decisively. Statistically significant differences between active treatment and placebo could also be shown for ankle mobility (neutral zero method) and global efficacy. Under active treatment, no adverse drug reactions were reported, and good local and global tolerance of the trial medication was confirmed.
A separate observer-blind, randomized, multicenter study (CODEC_2004) directly compared comfrey root extract ointment with diclofenac gel: in a single-blind, controlled, randomized, parallel-group, multicenter, and confirmatory clinical trial, outpatients with acute unilateral ankle sprains (n = 164, mean age 29.0 years, 47.6% female) received either a 6 cm long ointment layer of Kytta-Salbe f (comfrey extract) (n = 82) or diclofenac gel (n = 82) for 7 ± 1 days, four times a day.
In a controlled, double-blind, randomized, multicentre study, the efficacy and safety of the topical comfrey product Traumaplant® (10% active ingredient of a 2.5:1 aqueous ethanolic pressed juice of freshly harvested, cultivated comfrey herb [Symphytum × uplandicum Nyman], corresponding to 25 g of fresh herb per 100 g of cream; n = 104) was tested against a 1% product (corresponding to 2.5 g of fresh comfrey herb in 100 g of cream; n = 99) in 203 patients with acute ankle distortion. With the high concentration, decrease of the scores for pain on active motion, pain at rest, and functional impairment was highly significant and clinically relevant on days T3–4 as well as T7, and overall tolerability was excellent.
5.4 Knee Osteoarthritis
A randomised, double-blind, bicenter, placebo-controlled clinical trial investigated the effect of a daily application of 6 g Kytta-Salbe® f (3 × 2 g) over a 3-week period with patients suffering from painful osteoarthritis of the knee. The 220 patients examined consisted of 153 women and 67 men of an average age of 57.9 years. On average, the complaints relating to osteoarthritis of the knee had persisted for 6.5 years. Significant superiority (p < 0.001) of the verum group over the placebo group was proven in quality of life, angle measurement (mobility of the knee), clinical global impression, and global assessment of efficacy by both physician and patient. The results suggest that the comfrey root extract ointment is well suited for the treatment of osteoarthritis of the knee: pain is reduced, mobility of the knee improved, and quality of life increased.
5.5 Musculoskeletal Rheumatism (Epicondylitis, Tendovaginitis, Periarthritis)
In an earlier 4-week pilot study, 41 patients with different forms of musculoskeletal rheumatism (mainly epicondylitis, tendovaginitis, and periarthritis) were treated topically with comfrey cream (n = 20) or with placebo (n = 21). Efficacy was assessed using several pain parameters: tenderness when pressure applied, pain at rest, and during exercise. With respect to "tenderness when pressure applied," the ointment proved superior to placebo in patients with epicondylitis and tendovaginitis, but not in patients with periarthritis.
5.6 Anti-inflammatory Activity (Pharmacological Studies)
The effects of dermatological preparations containing 5% or 10% of a comfrey root extract on the process of healing of experimentally induced UV-B erythema were studied in 29 volunteers in a controlled pharmacological trial. The anti-inflammatory potency of the extract was found to be equal to or greater than that of diclofenac.
5.7 Use in Children
The efficacy and safety of Symphytum cream in children was reviewed and confirmed in an observational study. In this study, 196 four- to 12-year-old children diagnosed with blunt trauma had comfrey ointment applied to the affected areas three times a day. To assess efficacy, palpitation pain, functional disability, edema, and hematoma were considered. The mean treatment duration was 7.6 ± 1.1 days. Remission rates for the criteria assessed were 86.3% for palpitation pain, 86.7% for movement pain, 89.7% for functional disability, 94% for edema, and 90.1% for general disability. No adverse drug reactions were observed.
Overall Evidence Strength for Topical Use
Today, multiple randomized controlled trials have demonstrated the efficacy and safety of comfrey preparations for the topical treatment of pain, inflammation and swelling of muscles and joints in degenerative arthritis, acute myalgia in the back, sprains, contusions, and strains after sports injuries and accidents, also in children aged 3 or 4 and over. The quality of the evidence base for topical musculoskeletal use is moderate-to-good, comprising multiple double-blind, randomized, placebo-controlled, or active-comparator-controlled trials; however, most were conducted or funded in connection with specific commercial preparations and sample sizes were modest. No clinical-pharmacokinetic investigation results in humans have been published so far on the absorption, distribution, and elimination of the constituents of comfrey extracts.
The German Commission E has assessed Symphyti radix (comfrey root) deriving from Symphytum officinale L. positively for the external use in bruises, strains, and sprains, and acknowledged its actions as anti-inflammatory, antimitotic, and promotion of callus formation. A European Scientific Cooperative on Phytotherapy (ESCOP) monograph is also available for comfrey root. The monograph mentions strains, contusions and distortions, osteoarthritis, epicondylitis, tendovaginitis, and periarthritis as therapeutic indications substantiated by clinical trials.
6. Body Systems and Health Areas
- Musculoskeletal system: The primary area of documented clinical use. Comfrey root extract has been used for the topical treatment of painful muscle and joint complaints. It is clinically proven to relieve pain, inflammation and swelling of muscles and joints in the case of degenerative arthritis, acute myalgia in the back, sprains, contusions, and strains after sports injuries and accidents, also in children aged 3 years and older.
- Integumentary system (skin and wound healing): The therapeutic properties of comfrey stimulate granulation and support tissue regeneration. Comfrey root extract has demonstrated an antimicrobial effect on Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa in laboratory studies, though the clinical relevance of this finding is not established.
- Gastrointestinal system (historical, internal use no longer recommended): For internal application, it was historically claimed to be beneficial for gastritis, ulcers, diarrhoea, and various allergies including asthma; the pyrrolizidine content of comfrey products varies greatly, and hepatic toxicity is largely associated with daily intake of tablets or multiple cups of tea.
- Hepatic system (adverse effects): Comfrey has been used as a herbal to treat wounds and to decrease pain and inflammation associated with arthritis, sprains and bone fractures. Comfrey, however, also contains pyrrolizidine alkaloids and, when taken orally, can cause sinusoidal obstruction syndrome and severe liver injury.
7. Dosage Forms and Dosages Reported in Studies
Topical Preparations (as reported in clinical studies and regulatory documents)
- Ointments and creams: Ointment containing Symphytum root 10–15% root extractive in usual type ointment basis applied topically. Although internal use of comfrey is no longer advised, dosages for oral administration for traditional uses were recommended in older standard herbal reference texts.
- Back pain trials: One double-blind, placebo-controlled, multicentre, randomized clinical trial was conducted over a period of 5 days. 120 patients with acute upper or lower back pain were treated three times a day, 4 g per application.
- Ankle sprain trials: Patients received either a 6 cm long ointment layer of Kytta-Salbe f (comfrey extract) or diclofenac gel for 7 ± 1 days, four times a day.
- Knee osteoarthritis trial: A daily application of 6 g Kytta-Salbe® f (3 × 2 g) over a 3-week period was used.
- Traumaplant® (wound healing): 10% active ingredient of a 2.5:1 aqueous ethanolic pressed juice of freshly harvested, cultivated comfrey herb (Symphytum × uplandicum Nyman), corresponding to 25 g of fresh herb per 100 g of cream.
EMA-Regulated Daily PA Exposure Limit
The European Medicines Agency (EMA) permits only the external use of comfrey root (Symphyti radix), directly on intact skin in short-term treatments (up to 10 days) and limiting the supply of PA to 0.007 μg/kg (0.35 μg/day).
Historical Oral Dosages (no longer recommended)
Although internal use of comfrey is no longer advised, dosages for oral administration for traditional uses were recommended in older standard herbal reference texts. The British Herbal Pharmacopoeia (1974 and 1983) for the treatment of gastric and duodenal ulcer, colitis, and hematemesis listed: Root, liquid extract: 2–4 ml (1983 edition) or 2–8 ml (1974 edition) (1:1 in 25% alcohol).
8. Safety Considerations and Regulatory Status
8.1 Pyrrolizidine Alkaloid Hepatotoxicity
Pyrrolizidine alkaloids (PAs) are common secondary plant compounds with hepatotoxicity. The consumption of herbal medicines and herbal teas containing PAs is one of the main causes of hepatic sinusoidal obstruction syndrome (HSOS), a potentially life-threatening condition.
Comfrey also contains several pyrrolizidine alkaloids (symphytine, echimidine, symglandine and lycopsamine) which are toxic and capable of causing sinusoidal obstruction syndrome (previously called veno-occlusive disease) and severe liver injury. Likelihood score for oral comfrey: C (a probable cause of clinically apparent liver injury due to sinusoidal obstruction syndrome).
A case report described one patient with hepatic veno-occlusive disease and severe portal hypertension, who subsequently died from liver failure after ingesting young comfrey leaves. The patient had been on a predominantly vegetarian diet and, prior to his illness, took comfrey leaves, which are known to contain hepatotoxic pyrrolizidine alkaloids.
The amount of pyrrolizidine alkaloids in comfrey varies by the part of the plant used, its age, and time of harvesting. The toxicity of pyrrolizidine-containing substances is increased by microsomal enzyme inducers such as phenobarbital.
8.2 Genotoxicity and Carcinogenicity
Results of a transgenic rat study indicate that comfrey is mutagenic in rat liver and the types of mutations induced by comfrey suggest that its tumorigenicity results from the genotoxicity of pyrrolizidine alkaloids in the plant. Comfrey has induced hepatic veno-occlusive disease in humans and hepatocellular adenomas and haemangioendothelial sarcomas in rat liver. Although there are no epidemiological data regarding the carcinogenicity of comfrey in humans, these adverse effects have raised questions of its potential carcinogenicity.
S. officinale extract and the components lasiocarpine and symphytine are carcinogenic in rats, possibly via genotoxic mechanisms; however, an association of comfrey consumption with cancer in humans is lacking.
8.3 Topical Absorption of Pyrrolizidine Alkaloids
The only studies on the penetration of PAs (mainly lycopsamine) through human skin show a low permeability, below 1% but up to 4.9% in the "worst case" scenario. Although systemic absorption following use of topical comfrey preparations is not fully known, an evaluation in human skin samples suggests there may be an overestimation of risk for pyrrolizidine alkaloid absorption. The recommendation of the European Medicines Agency (EMA) for the limit of external medicinal application is based on the limit originally determined for oral use and proposes that the amount of toxic, unsaturated PAs within the daily dose should be < 0.35 μg and the use should be restricted to intact skin.
8.4 Regulatory Actions
On July 6, 2001, the Food and Drug Administration issued a letter to industry communicating concern about the safety of supplement products containing comfrey, advising that, because comfrey contains certain toxic substances — pyrrolizidine alkaloids — that have been associated with liver damage and other health hazards, it should not be used as an ingredient in supplements. FDA further recommended that firms immediately stop marketing comfrey-containing supplements.
In the US, the Food and Drug Administration (FDA) in 2001 ordered the withdrawal of all dietary supplements containing comfrey, but it can still be found as an ingredient in some cosmetics.
Due to hepatotoxic pyrrolizidine alkaloids (PAs), the EMA restricts the use of comfrey root to external use only and for short periods of time. The European Medicines Agency does not permit comfrey for internal use; external use is restricted to adults only, for a maximum duration of 10 days, and the PA content of the preparation must not exceed 0.35 mcg per day.
In some countries, such as Germany, Hungary, and Austria, products with comfrey root from which the pyrrolizidine alkaloids have been removed in the process of manufacturing the herbal product are available.
The German Federal Health Office has restricted the availability of botanical medicines containing unsaturated pyrrolizidine alkaloids. In Germany, the use of comfrey is limited to external products and the maximal permissible dose of PA is 100 μg/d with a duration of treatment limited to between 4 and 6 weeks per year.
In the UK, the National Institute of Medical Herbalists (NIMH) has imposed a self-regulated ban restricting comfrey root to external use only, and a self-regulated restriction on comfrey leaf to 100 ml (1:5) tincture for a maximum of six weeks' use. The American Botanical Council has approved use of both leaf and root for external use only, restricted to a daily dose of 100 mcg, for no longer than 4–6 weeks per year.
8.5 Contraindications and Special Populations
Use is contraindicated during pregnancy and lactation, in infants, and in patients with liver or kidney disease. This is contraindicated because of documented adverse effects. Pyrrolizidine alkaloids have abortifacient effects and increase the risk of fatal hepatic veno-occlusive disease. Infants are more susceptible to pyrrolizidine-related veno-occlusive disease; therefore, the use of comfrey in this population is contraindicated. Animal experiments have detected alkaloids in breast milk.
In deep wounds, comfrey can cause tissue to form over the wound before deeper healing is finished, resulting in abscesses.
8.6 Drug Interactions
The toxicity of pyrrolizidine-containing substances is increased by microsomal enzyme inducers such as phenobarbital. Beyond this pharmacological interaction, no well-documented drug–drug interactions for topical comfrey preparations are reported in the peer-reviewed literature reviewed here.
References
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