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Comfrey

Medically reviewed by Drugs.com. Last updated on Jan 17, 2019.

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

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

  • Boraginaceae (Borage)

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 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

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. Experimental evidence exists of the potentiation of toxicity of comfrey's alkaloids by phenobarbital via the cytochrome P450 pathway.Stickel 2000

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

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

Ahmad VU, Noorwala M, Mohammad FV, Sener B. A new triterpene glycoside from the roots of Symphytum officinale. J Nat Prod. 1993;56(3):329-334.8482944
Andres R, Brenneisen R, Clerc JT. Relating antiphlogistic efficacy of dermatics containing extracts of Symphytum officinale to chemical profiles. Planta Med. 1989;55(7):643-644.
Awang DV. Comfrey. Can Pharm J. 1987;120:101-104.
Barna M, Kucera A, Hladícova M, Kucera M. Wound healing effects of a Symphytum herb extract cream (Symphytum x uplandicum NYMAN: ): results of a randomized, controlled double-blind study [in German]. Wien Med Wochenschr. 2007;157(21-22):569-574.18157595
Benedek B, Ziegler A, Ottersbach P. Absence of mutagenic effects of a particular Symphytum officinale L. liquid extract in the bacterial reverse mutation assay. Phytother Res. 2010;24(3):466-468.19827020
Brinker FJ. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications;1998.
Cameron M, Chrubasik S. Topical herbal therapies for treating osteoarthritis. Cochrane Database Syst Rev. 2013;(5):CD010538.23728701
Dolganiuc A, Radu LD, Olinescu A. The effect of products of plant and microbial origin on phagocytic function and on the release of oxygen free radicals by mouse peritoneal macrophages [in Romanian]. Bacteriol Virusol Parazitol Epidemiol. 1997;42(1-2):65-69.9235147
Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG. 2002;109(3):227-235.11950176
Franz G. Polysaccharides in pharmacy: current applications and future concepts. Planta Med. 1989;55(6):493-497.2694198
Frost R, MacPherson H, O'Meara S. A critical scoping review of external uses of comfrey (Symphytum spp.). Complement Ther Med. 2013;21(6):724-745.24280482
Furuya T, Hikichi M. Alkaloids and triterpenoids of Symphytum officinale. Phytochemistry. 1971;10(9):2217-2220.
Gagnier JJ, Oltean H, van Tulder MW, Berman BM, Bombardier C, Robbins CB. Herbal medicine for low back pain: A Cochrane review. Spine (Phila Pa 1976). 2016;41(2):116-133.26630428
Giannetti BM, Staiger C, Bulitta M, Predel HG. Efficacy and safety of comfrey root extract ointment in the treatment of acute upper or lower back pain: results of a double-blind, randomised, placebo controlled, multicentre trial. Br J Sports Med. 2010;44(9):637-641.19460762
Gomes MF, de Oliveira Massoco C, Xavier JG, Bonamin LV. Comfrey ( Symphytum Officinale. L.) and experimental hepatic carcinogenesis: a short-term carcinogenesis model study. Evid Based Complement Alternat Med. 2010;7(2):197-202.18955295
Grube B, Grünwald J, Krug L, Staiger C. Efficacy of a comfrey root (Symphyti offic. radix) extract ointment in the treatment of patients with painful osteoarthritis of the knee: results of a double-blind, randomised, bicenter, placebo-controlled trial. Phytomedicine. 2007;14(1):2-10.17169543
Györik S, Stricker H. Severe pulmonary hypertension possibly due to pyrrolizidine alkaloids in polyphytotherapy. Swiss Med Wkly. 2009;139(13-14):210-211.19350428
Hirono I, Haga M, Fujii M, et al. Induction of hepatic tumors in rats by senkirkine and symphytine. J Natl Cancer Inst. 1979;63(2):469-472. 287835
Hirono I, Mori H, Haga M. Carcinogenic activity of Symphytum officinale. J Natl Cancer Inst. 1978;61(3):865-869.278864
Karavaev VA, Solntsev MK, Iurina TP, Iurina EV, Poliakova IB, Kuznetsov AM. Antifungal activity of aqueous extracts of the leaves of cowparsnip and comfrey [in Russian]. Izv Akad Nauk Ser Biol. 2001;4:435-441.11525124
Koll R, Buhr M, Dieter R, et al. Efficacy and tolerance of a comfrey root extract (Extr. Rad. Symphyti) in the treatment of ankle distorsions: results of a multicenter, randomized, placebo-controlled, double-blind study. Phytomedicine. 2004;11(6):470-477.15500257
Koll R, Klingenburg S. Therapeutic characteristance and tolerance of topical comfrey preparations. Results of an observational study of patients [in German]. Fortschr Med Orig. 2002;120(1):1-9.14518351
Kucera M, Barna M, Horácek O, Kováriková J, Kucera A. Efficacy and safety of topically applied Symphytum herb extract cream in the treatment of ankle distortion: results of a randomized controlled clinical double blind study. Wien Med Wochenschr. 2004;154(21-22):498-507.15638067
Kucera M, Kálal J, Polesná Z. Effects of Symphytum ointment on muscular symptoms and functional locomotor disturbances. Adv Ther. 2000;17(4):204-210.11185060
Kumana CR, Ng M, Lin HJ, Ko W, Wu PC, Todd D. Hepatic veno-occlusive disease due to toxic alkaloid herbal tea. Lancet. 1983;2(8363):1360-1361.6139688
Kucera M, Barna M, Horàcek O, Kàlal J, Kucera A, Hladìkova M. Topical symphytum herb concentrate cream against myalgia: a randomized controlled double-blind clinical study. Adv Ther. 2005;22(6):681-692.16510384
Larrey D. Liver involvement in the course of phytotherapy [in French]. Presse Med. 1994;23(15):691-693.8072973
Mattocks AR. Toxicity of pyrrolizidine alkaloids. Nature. 1968;217(5130):723-728.5641123
Mattocks AR. Toxic pyrrolizidine alkaloids in comfrey. Lancet. 1980;2(8204):1136-1137.6107747
Mei N, Guo L, Fu PP, Heflich RH, Chen T. Mutagenicity of comfrey ( Symphytum Officinale) in rat liver. Br J Cancer. 2005;92(5):873-875.15726100
Mutterlein R, Arnorld CG. Investigations concerning the content and the pattern of pyrrolizidine alkaloids in Symphytum officinale L. (comfrey). Pharm Ztg Wiss. 1993;138(5/6):119-125.
Newall CA, Anderson LA, Phillipson JD, eds. Herbal Medicines: A Guide for Health-Care Professionals. London: Pharmaceutical Press; 1996.
Olinescu A, Manda G, Neagu M, Hristescu S, Dasanu C. Action of some proteic and carbohydrate components of Symphytum officinale upon normal and neoplastic cells. Roum Arch Microbiol Immunol. 1993;52(2):73-80.8186457
Oltean H, Robbins C, van Tulder MW, Berman BM, Bombardier C, Gagnier JJ. Herbal medicine for low-back pain. Cochrane Database Syst Rev. 2014;(12):CD004504.25536022
Panter KE, James LF. Natural plant toxicants in milk: a review. J Anim Sci. 1990;68(3):892-904.2180885
Predel HG, Giannetti B, Koll R, Bulitta M, Staiger C. Efficacy of a comfrey root extract ointment in comparison to a diclofenac gel in the treatment of ankle distortions: results of an observer-blind, randomized, multicenter study. Phytomedicine. 2005;12(10):707-714.16323288
Ridker PM, Ohkuma S, McDermott WV, Trey C, Huxtable RJ. Hepatic venocclusive disease associated with the consumption of pyrrolizidine-containing dietary supplements. Gastroenterology. 1985;88(4):1050-1054.3972224
Rode D. Comfrey toxicity revisited. Trends Pharmacol Sci. 2002;23(11):497-499.12413798
Schoental R. Health hazards of pyrrolizidine alkaloids: a short review. Toxicol Lett. 1982;10(4):323-326.7046139
Shipochliev T. Uterotonic action of extracts from a group of medicinal plants [in Bulgarian]. Vet Med Nauki. 1981;18(4):94-98.7314446
Staiger C. Comfrey root: from tradition to modern clinical trials. Wien Med Wochenschr. 2013;163(3-4):58-64.23224633
Stewart MJ, Steenkamp V. Pyrrolizidine poisoning: a neglected area in human toxicology. Ther Drug Monit. 2001;23(6):698-708.11802107
Stickel F, Seitz HK. The efficacy and safety of comfrey. Public Health Nutr. 2000;3(4a):501-508.11276298
Svoboda DJ, Reddy JK. Malignant tumors in rats given lasiocarpine. Cancer Res. 1972;32(5):908-913.4336029
Symphytum officinale L. USDA, NRCS. 2017. The PLANTS Database (http://plants.usda.gov, August 2017). National Plant Data Center, Baton Rouge, LA 70874-4490 USA.
Tunón H, Olavsdotter C, Bohlin L. Evaluation of anti-inflammatory activity of some Swedish medicinal plants. Inhibition of prostaglandin biosynthesis and PAF-induced exocytosis. J Ethnopharmacol. 1995;48(2):61-76.8583796
Tyler VE. The Honest Herbal. 3rd ed. New York, NY: Pharmaceutical Press; 1972.
U.S. Food and Drug Administration. Center for Food Safety and Applied Nutrition. FDA advises dietary supplement manufacturers to remove comfrey products from the market. July 6, 2001. http://www.cfsan.fda.gov/~dms/dspltr06.html. Accessed January 10, 2006
Wagner H, Hörhammer L, Frank U. Lithospermic acid, the antihormonally active principle of Lycopus europaeus L. and Symphytum officinale 3. Ingredients of medicinal plants with hormonal and antihormonal-like effect [in German]. Arzneimittelforschung. 1970;20(5):705-713.4193311
Yeong ML, Clark SP, Waring JM, Wilson RD, Wakefield SJ. The effects of comfrey derived pyrrolizidine alkaloids on rat liver. Pathology. 1991;23(1):35-38.2062566
Yeong ML, Swinburn B, Kennedy M, Nicholson G. Hepatic veno-occlusive disease associated with comfrey ingestion. J Gastroenterol Hepatol. 1990;5(2):211-214.2103401

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