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Comfrey

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

Medically reviewed by Drugs.com. Last updated on Jan 15, 2024.

Clinical Overview

Use

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.

Dosing

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.

Contraindications

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.

Pregnancy/Lactation

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.

Interactions

None well documented.

Adverse Reactions

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.

Toxicology

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.

Scientific Family

Botany

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

History

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

Chemistry

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

Large amounts of mucilage, fructanes, and starch are found in the leaves and rootsGiannetti 2010, Koll 2004 while a pentacyclic triterpene glycoside of oleanolic acid was identified in the root.Ahmad 1993, Wagner 1970

Uses and Pharmacology

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.

Antifungal activity

Aqueous extracts from comfrey leaves strongly inhibited plant pathogenic fungi, most likely because of the plant's phenolic compounds.Karavaev 2001

Cancer

Various extracts and fractions of S. officinale have inhibited tumor cell proliferation and exerted antimitotic effects in animal and in vitro experiments.Yeong 2001, Awang 1987, Gomes 2010, Olinescu 1993

Hormonal

Lithospermic acid isolated from the root appears to have antigonadotropic activity.Wagner 1970

Inflammation

Clinical data

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

Lower back pain

Clinical data

A systematic review evaluated randomized trials of various herbal therapies in patients with acute, subacute, and chronic low back pain. The review found that compared with placebo, the evidence for effectiveness was the best for topical Capsicum frutescens (cayenne), with some evidence for oral Harpagophytum procumbens (Devil's claw), oral Salix alba (white willow bark), topical Symphytum officinale (comfrey root extract), and topical lavender essential oil. However, there were methodologic limitations to the trials, outcomes assessed were short-term, and it is not clear how these treatments compare with over-the-counter analgesics.Oltean 2014

Wound healing

Clinical data

The use of a topical 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 Comfrey was one of the 3 most common herbs used by certified or licensed midwives for perineal healing and discomfort based on state-wide surveys in California, Texas, and North Carolina.Dennehy 2010

Dosing

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

Interactions

Case reports are lacking. Data exists of the potentiation of toxicity of comfrey's alkaloids by phenobarbital via the cytochrome P450 pathway.Stickel 2000

Comfrey drug interactions (more detail)

Adverse Reactions

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 systematic review of case studies published through November 2017 identified 8 cases of adverse reactions related to comfrey when combining keyword search terms for pyrrolizidine alkaloid-related harm and comfrey, S. officinale. Of the 8 cases, only 1 noted the absence of any other concomitant herbs and/or medications whereas 7 confirmed their presence. The case without concomitant herbs/medications documented fatal hepatoveno-occlusive disease in a 23-year-old male. In contrast to the WHO Uppsala Monitoring Center system that assigned a "probable" or "possible" likelihood to all 7 assessable cases, causality assessment by a toxicologist concluded the harm as unlikely related to comfrey in 3 cases, "possibly" related in 2 cases, and 1 additional case classified as unassessable.(Avila 2020)

The European Association for the Study of the Liver (EASL) clinical practice guideline for drug-induced liver injury (2019) recommends physicians consider herbal and dietary supplements as potential causative agents associated with liver injury (Level 4; Grade C), particularly those containing pyrrolizidine alkaloids such as comfrey, which has some of the highest levels of evidence supporting hepatotoxicity.(EASL 2019)

Toxicology

Carcinogenicity

S. officinale extract and components lasiocarpine and symphytine are carcinogenic in rats, possibly via genotoxic mechanismsSvoboda 1972, Hirono 1979, Hirono 1978, Mei 2005; however, an association of comfrey consumption with cancer in humans is lacking.Stickel 2000

A pyrrolizidine alkaloid-free liquid extract of comfrey root was not mutagenic when tested by the bacterial reverse mutation assay.Benedek 2010

Hepatotoxic effects

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

References

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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