Scientific Name(s): S. asperum Lepechin, S. tuberosum L., Symphytum officinale L., Symphytum x uplandicum Nyman Common Name(s): Blackwort, Bruisewort, Comfrey, Knitbone, Radix consolidate, Russian comfrey, Slippery root, Symphyti radix
Therapeutic use of comfrey is limited because of its toxicity. A limited number of clinical trials show short-term efficacy of topically applied, alkaloid-free comfrey preparations in skin abrasions and inflammatory conditions. Although not examined in clinical trials, comfrey may possess antifungal and anticancer activity.
Oral use of comfrey is not supported because of potential hepatotoxicity. Additionally, because externally applied alkaloids are well absorbed and detected in the urine, topical use of comfrey should not exceed an alkaloid exposure of 100 mcg/day. Limited trials have evaluated the efficacy of alkaloid-free preparations for topical use; however, these studies do not report on hepatic laboratory indices of study participants.
Comfrey is not recommended for internal use because of the hepatotoxic pyrrolizidine alkaloid content. Patients with hypersensitivity or allergic reactions to the plant should avoid external use. Use is contraindicated during pregnancy and lactation, in infants, and in patients with liver or kidney disease.
Contraindicated because of documented adverse effects. Pyrrolizidine alkaloids have abortifacient effects and increase the risk of fatal hepatic veno-occlusive disease. Animal experiments have detected alkaloids in breast milk.
None well documented.
Neither internal nor extensive topical use of comfrey is recommended because of numerous reports of liver toxicity (see Toxicology). Case reports show hepatic veno-occlusive disease and pulmonary hypertension related to comfrey use. Infants are more susceptible to pyrrolizidine-related, veno-occlusive disease; therefore, the use of comfrey in this population is contraindicated.
The Food and Drug Administration (FDA) released an advisory in July 2001 recommending that comfrey products be removed from the market because of cases of hepatic veno-occlusive disease. Comfrey is generally considered unsafe, with numerous toxicological effects in animals and humans.
Comfrey is a perennial plant found in moist grasslands in western Asia, as well as in North America. It grows to heights of 50 to 150 cm and has long, hairy lanceolate leaves and bell-shaped, red-violet or yellowish flowers. S. x uplandicum Nyman is a hybrid of S. officinale and S. asperum, and has been cultivated to contain insignificant amounts of alkaloids in the aerial parts of the plant.Kucera 2005, PLANTS 2017, Stickel 2000
Comfrey has been cultivated in Japan as a green vegetable and has been used as an herbal medicine for more than 2,000 years. Comfrey's original name, knitbone, derives from the external use of poultices of its leaves and roots to heal burns, sprains, swelling, and bruises. In Western Europe, comfrey has been used topically for treating inflammatory disorders such as arthritis, gout, and thrombophlebitis, and internally for treating diarrhea. Comfrey has been claimed to heal gastric ulcers and hemorrhoids, and to suppress bronchial congestion and inflammation. Symphyti radix (comfrey root) is recommended in the German Commission E Monographs for external use in bruises and sprains.Staiger 2013, Stewart 2001, Stickel 2000
Numerous hepatotoxic pyrrolizidine alkaloids with differing toxicities have been identified in the plant, including symphytine, echimidine, intermedine, symviridine, and lasiocarpine (retronecine mono- and diester alkaloids). Roots contain a 100-fold higher alkaloid content than the aerial portions.Furuya 1971, Rode 2002, Stickel 2000
The healing action of poultices of comfrey roots and leaves may be related to the presence of allantoin. The underground roots contain allantoin 0.6% to 0.7% and tannin 4% to 6.5%; the leaves contain a higher proportion of tannin relative to allantoin. The roots also contain rosmarinic and lithspermic acid.Ahmad 1993, Mutterlein 1993, Tyler 1972, Wagner 1970
The therapeutic use of comfrey is due in part to allantoin and rosmarinic acid content, but it is limited by the toxicity of pyrrolizidine alkaloids.Stewart 2001 Controlled cultivation of S. x uplandicum is said to produce a plant devoid of the toxic alkaloids in the aerial plats, enabling the production of relatively nontoxic comfrey preparations.Kucera 2005 Pyrrolizidine alkaloid-free preparations of comfrey have been used in clinical studies in Germany.
Aqueous extracts from comfrey leaves strongly inhibited plant pathogenic fungi, most likely because of the plant's phenolic compounds.Karavaev 2001
Lithospermic acid isolated from the root appears to have antigonadotropic activity.Wagner 1970
A limited number of clinical trials have been conducted to assess the efficacy of topically applied, alkaloid-free comfrey preparations in ankle sprains, osteoarthritic knee conditions, and back pain/myalgia. Critical reviews of clinical trials have been published.Cameron 2013, Frost 2013, Gagnier 2016 Outcome measures include patient assessment of pain and mobility, as well as measures of ankle swelling and clinician evaluations. Most studies show a statistically significant advantage of active preparation over placebo in the short term; however, because many of these trials have been conducted by product manufacturers, the possibility of publishing bias exists.Cameron 2013, Frost 2013, Gagnier 2016 Other open-label or single-blind trials with topical comfrey preparations have been conducted; however study design limits the validity of the results.Koll 2002, Kucera 2000, Predel 2005 Preparations generally contained a 35% liquid root extract from which toxic alkaloids were removed and standardized to allantoin 0.2% to 0.5%Giannetti 2010, Grube 2007, Koll 2004, Predel 2005 or to a preparation with 10% extract of S. x uplandicum aerial parts.Kucera 2005, Kucera 2004 Duration of use ranged from 5 days to 3 weeks in these studies. The studies report no adverse effects, although liver function test results were not reported.
Mechanisms of action include effects on platelet activating factor, as well as on the synthesis of the enzymes catalase and superoxide dimutase.Dolganiuc 1997, Tunón 1995
The use of a dermal preparation of comfrey derived from alkaloid-free cultivars of S. x uplandicum has been studied in limited clinical trials. Applied to fresh abrasions, a 10% preparation showed faster decreases in wound size and shorter times to healing, with no cutaneous reactions to the preparation reported.Barna 2007, Kucera 2005 The preparations were applied to the skin over short time periods (days) only. Efficacy in wound healing may be related to the presence of allantoin, rosmarinic acid, or another hydrocolloid polysaccharide.Andres 1989, Franz 1989
The oral use of comfrey cannot be supported because of potential hepatotoxicity. Because externally applied alkaloids are well absorbed (detected in the urine), topical use of comfrey should not exceed an alkaloid exposure of 100 mcg/day.Staiger 2013, Stickel 2003
Limited trials have evaluated the efficacy of alkaloid-free preparations for topical use; however, these studies do not report on hepatic laboratory indices of the participants.
Pregnancy / Lactation
Avoid use because of documented adverse effects. Pyrrolizidine alkaloids have abortifacient effects and increase the risk of fatal hepatic veno-occlusive disease.Brinker 1998, Ernst 2002, Newall 1996 An extract of S. officinale has been reported to enhance uterine tone.Shipochliev 1981 Animal experiments have detected comfrey alkaloids in breast milk.Panter 1990, Schoental 1982
Case reports are lacking. Experimental evidence exists of the potentiation of toxicity of comfrey's alkaloids by phenobarbital via the cytochrome P450 pathway.Stickel 2000
Neither internal nor extensive topical use of comfrey can be recommended because of numerous reports of liver toxicity (see Toxicology). Case reports show hepatic veno-occlusive disease and pulmonary hypertension related to comfrey use.Stickel 2000, Györik 2009 Infants are more susceptible to pyrrolizidine-related, veno-occlusive disease; therefore, the use of comfrey in this population is contraindicated.Stickel 2000
A pyrrolizidine alkaloid-free liquid extract of comfrey root was not mutagenic when tested by the bacterial reverse mutation assay.Benedek 2010
The FDA released an advisory in July 2001 recommending that comfrey products be removed from the market following several cases of hepatic veno-occlusive disease in which the destruction or obliteration of small hepatic veins led to cirrhosis and, eventually, liver failure. Also in 2001, the Federal Trade Commission brought enforcement action against a company marketing comfrey-containing products. The parties agreed to a preliminary injunction that prohibited the company from marketing any comfrey-containing products intended for internal use or use on open wounds, as well as requiring a warning on comfrey products intended for external use.FDA 2006, Mattocks 1990, Ridker 1985, Larrey 1994, Kumana 1983, Yeong 1990, Mattocks 1968
Human poisonings with pyrrolizidine alkaloids are usually accidental and may be caused by ingestion of contaminated flour, milk, certain goat products that are resistant to the alkaloids, honey produced by bees fed on pyrrolizidine-containing weeds, and consumption of certain herbal or bush teas. It also may be caused by comfrey used in salads.Stewart 2001, Rode 2002, Schoental 1982, Panter 1990
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