DRUGS AND SUPPLEMENTS

Comfrey (Symphytum spp.)

March 22, 2017

../../images/ss_comfrey.jpg

Comfrey (Symphytum spp.)

Natural Standard Bottom Line Monograph, Copyright © 2013 (www.naturalstandard.com). Commercial distribution prohibited. This monograph is intended for informational purposes only, and should not be interpreted as specific medical advice. You should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.

While some complementary and alternative techniques have been studied scientifically, high-quality data regarding safety, effectiveness, and mechanism of action are limited or controversial for most therapies. Whenever possible, it is recommended that practitioners be licensed by a recognized professional organization that adheres to clearly published standards. In addition, before starting a new technique or engaging a practitioner, it is recommended that patients speak with their primary healthcare provider(s). Potential benefits, risks (including financial costs), and alternatives should be carefully considered. The below monograph is designed to provide historical background and an overview of clinically-oriented research, and neither advocates for or against the use of a particular therapy.

Related Terms

  • 7-Acetylintermedine, acetyllcopsamine, allantoin, allantoin-beta-cyclodextrin, anadoline, asperum polymer, ass ear, assear, asses-ears, Beinwell (German), black root, black wort, blackwort, blue comfrey, bocking 14, boneset, Boraginaceae (family), Borago-Symphytum, borraja, bourrache, bruisewort, bulbous comfrey, buyuk karakafesotu, Caucasian comfrey, comfrey extract, comfrey herb, comfrey root, common comfrey, comphrey, consolida, consolida aspra (Italian), consolidae radix, consolida majoris, consolide maggiore (Italian), consormol, consoude, consoude grande (French), consoude rude (French), consound, consuelda (Spanish), creeping comfrey, Crimean comfrey, echimidine, Extr. Rad. Symphyti, glucofructan, great comfrey, ground comfrey root, gum plant, healing blade, healing herb, heliotrine, hirehari-so, hydroxycinnamate-derived polymer, integerrimine, intermedine, knitback, knitbone, Kytta-Balsam® f, Kytta-Plasma® f, Kytta-Salbe® f, lasiocarpine, liane chique, lithospermic acid, lycopsamine, medicinal comfrey, mucopolysaccharides, navadni gabez (Slovenian), nipbone, okopnik sherohovaty (Russian), oreille d'ane (French), otonecine- pyrrolizidine alkaloids, prickley comfrey, pyrrolizidine alkaloid, Quaker comfrey, radix symphyti, rauher Beinwell (German), rauhe Wallwurz (German), Reinweld (German), retronecine, retrorsine, retrorsine N-oxide, riddelliine, ridelliine N-oxide, rosmarinic acid, rough comfrey, ru kulsukker (Danish), Russian comfrey, ruwe smeerworted (Dutch), salsify, saponins, senecionine, senecionine N-oxide, seneciphylline, senkirkine, simfit (Italian), slippery root, S. x uplandicum, symlandine, symphyti herba, symphyti folium, symphyti radix, symphytine, symphytum alkaloids, Symphytum asperrimum Donn, Symphytum asperum, Symphytum asperum Lepechin, Symphytum asperum x officinale, Symphytum bulbosum, Symphytum caucasicum, Symphytumcaucasicvum, Symphytum cream, Symphytumgrandiflorum, Symphytumibericum, Symphytum officinale Linn, Symphytum orientale,Symphytum peregrinum Lebed, Symphytum radix, Symphytum spp., Symphytum tauricum, Symphytum tuberosum, Symphytum x, Symphytum x uplandicum, Symphytum x uplandicum Nyman, Syrupus de Symphyto (Spanish), tannins, tarharaunioyrtti (Finnish), the great comfrey, tuberous comfrey, 7- uplandine, wallwort, wallwurz (German), white comfrey, yalluc (Saxon), zinzinnici (Italian).

Background

  • Comfrey (Symphytum spp.) is native to both Europe and Asia and has traditionally been used as both a food and forage crop. Three plant species in the genus Symphytum are medicinally relevant and include wild or common comfrey (Symphytum officinale L.), prickly or rough comfrey [Symphytum asperum Lepechin (Symphytum asperrimum Donn)], and Caucasian, Quaker, Russian, or blue comfrey [Symphytum × uplandicum Nyman (Symphytum peregrinum Lebed.)], which originated as a natural hybrid of Symphytum officinale L. and Symphytum asperum Lepechin.

  • Comfrey has traditionally been both applied to the skin (topically) for inflammation, pain and wound healing, and taken by mouth (orally) for gastrointestinal, respiratory and gynecological concerns.

  • Although evidence supporting oral use of comfrey is lacking, clinical trials suggest topical comfrey may be advantageous for pain and inflammation associated with injuries.

  • Although comfrey has been traditionally used both orally and topically, recent evidence suggesting carcinogenic and hepatotoxic effects has led to withdrawal of oral products from the market in many countries and warnings to avoid use on open wounds.

Scientific Evidence

Uses

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Grade*

Inflammation

Comfrey may have anti-inflammatory effects. Clinical trials investigating topical application of comfrey-containing creams have found significant reductions in inflammation and pain associated with sprains and muscle injuries. Additional study is needed to confirm these results.

B

Pain

Comfrey may have anti-inflammatory effects. Clinical trials investigating topical application of comfrey-containing creams have found significant reductions in inflammation and pain associated with sprains and muscle injuries. Additional study is needed to confirm these results.

B

Myalgia

A comfrey-containing cream has been applied on the skin to reduce pain associated with myalgia. Improvements in pain at rest and in motion were noted. Further studies are required before a firm recommendation can be made.

C

*Key to grades:A: Strong scientific evidence for this use; B: Good scientific evidence for this use; C: Unclear scientific evidence for this use; D: Fair scientific evidence against this use (it may not work); F: Strong scientific evidence against this use (it likely does not work).

Tradition/Theory

The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious and should be evaluated by a qualified health care professional.

  • Acne, aging, analgesic (pain reliever), anemia, angina (chest pain), antifungal, anti-inflammatory, antimicrobial, antioxidant, antipyretic (fever reducer), arthritis, broken bones, bronchitis, bruises, burns, cancer, conjunctivitis (pinkeye), cough, cough (bloody), dermatitis, diaper rash, diarrhea, expectorant (induces cough), eye infections (blepharitis), food uses, gangrene, gastritis, gout (foot inflammation), gum disease, gynecological disorders, hair tonic, hemorrhoids, hernia, high blood pressure, impetigo (pus-filled blisters), inflammatory bowel disease, lupus, mastitis (painful inflammation of breast), otitis (ear infection), pharyngitis, pleurisy (lung inflammation), rash, sexual arousal, sinusitis, skin disorders, sports injuries, sprains, thyroid disorders, tissue healing after surgery, ulcers, urine blood, uterine tonic, varicose veins, vasoprotective, wound healing.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older)

  • Due to safety concerns, taking comfrey by mouth is not recommended and oral sources cannot be sold in the United States. Traditional uses of comfrey include ingestion as an herbal tea. The 1990 German Commission E Monographs suggest maximal daily dose of 100 micrograms (external) unsaturated pyrrolidine alkaloids daily. The American Herbal Products Association's Botanical Safety Handbook from 1977 has similar recommendations.

  • Traditionally, a cloth or gauze soaked in an infusion (100 grams fresh, peeled root simmered in 250 milliliters water for 10-15 minutes) and applied to the skin several times daily has been used; duration was not noted. For a salve, olive oil and beeswax can be added and cooled.

Children (younger than 18 years)

  • There is no proven safe or effective dose for comfrey in children.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

  • Avoid in individuals with a known allergy or hypersensitivity to comfrey or its constituents.

Side Effects and Warnings

  • Comfrey is possibly safe when used as a cream applied to the skin for short-term (up to two weeks) treatment of minor injuries with no open wounds. Alkaloids may also be absorbed through intact skin, so precautions should still be taken. Use caution when using topical creams containing comfrey for extended periods.

  • Comfrey is likely unsafe when taken by mouth (orally) due to toxic pyrrolizidine alkaloids in comfrey. The U.S. Food and Drug Administration (FDA) has recommended removal of oral comfrey products from the market. Products made of comfrey root contain high levels of pyrrolizidine alkaloids.

  • Possible side effects associated with comfrey use include: abdominal pain, acute pneumonitis (inflammation of the lungs), ascites (accumulation of serous fluid in the abdominal cavity), Budd-Chiari syndrome (a rare liver disease in which a blood clot occurs in the large vein leading from the liver called the hepatic vein), cancer, damage to Disse's space, disruption of the sinusoidal wall, dose dependant liver damage, elevated serum transaminase levels, extravasation of red blood cells, heart problems, hemorrhagic necrosis, hepatic necrosis, hepatic veno-occlusive disease, hepatomegaly, jaundice, liver damage, liver failure, liver tumor induction, loss of definition of hepatocyte cellular membranes, loss of hepatocyte microvilli, loss of sinusoidal lining cells, obstructive ileus, occlusion of sub lobular veins, phytobezoar, platelets in areas of bleb formation around hepatocytes, severe portal hypertension, sinusoids filled with debris including cellular debris, hepatocyte organelles and red blood cells, skin redness, small venous radicles of the liver, swelling of hepatocytes, vascular congestion, venous endophlebitis, and zone 3 necrosis of hepatocytes.

  • Avoid oral comfrey due to hepatotoxic (liver damaging) and carcinogenic (cancer causing) pyrrolizidine alkaloids; oral use has caused death. Avoid topical comfrey in individuals with or at risk for hepatic disorders, cancer, or immune disorders due to potential for absorption of toxic compounds.

  • Use topical (applied to the skin) creams containing comfrey cautiously in patients using anti-inflammatory medications due to potential for additive effects.

  • Use cautiously in patients taking cytochrome P450 3A4-inducing agents, which may increase the conversion of compounds in comfrey to toxic metabolites.

Pregnancy and Breastfeeding

  • Avoid comfrey during pregnancy and breastfeeding as it may be hepatotoxic (liver damaging). Toxins from comfrey can be found in milk from grazing animals that have consumed comfrey. Thus it is likely that comfrey toxins would also be excreted in human breast milk.

Interactions

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.

Interactions with Drugs

  • Taking comfrey by mouth may increase the activity of the hepatic enzyme, aminopyrine N-demethylase.

  • Comfrey applied to the skin may offer anti-inflammatory effects. Caution is advised in patients taking anti-inflammatory medications due to possible additive effects.

  • Based on the potential for carcinogenic activity, oral (by mouth) or topically (applied to the skin) absorbed comfrey may have antagonistic effects to chemotherapeutic agents. Caution is advised when taking concurrently with other chemotherapeutic agents.

  • Agents that induce CYP3A4 may increase the conversion of compounds in comfrey to toxic metabolites.

  • Comfrey taken by mouth or applied to the skin may have additive adverse effects on the liver when used in combination with hepatotoxic (liver damaging) medications.

Interactions with Herbs and Dietary Supplements

  • Oral products containing comfrey leaf in combination with other ingredients were found to have lower total levels of alkaloids compared with bulk comfrey root or leaf.

  • Oral comfrey (Symphytum officinale) may increase the activity of the hepatic enzyme, aminopyrine N-demethylase.

  • Based on human study, topical comfrey may offer anti-inflammatory effects. Caution is advised in patients taking anti-inflammatory herbs, such as oral licorice or topical Ginkgo biloba, due to possible additive effects.

  • Based on the potential for carcinogenic activity, comfrey taken by mouth or applied to the skin may have antagonistic effects to chemotherapeutic agents. Caution is advised when taking concurrently with other herbs or supplements with potential chemotherapeutic effects.

  • Agents that induce CYP3A4 may increase the conversion of compounds in comfrey to toxic metabolites.

  • Oral or absorbed comfrey may have additive adverse effects on the liver when used in combination with hepatotoxic (liver damaging) herbs, such as kava, or supplements.

  • The combination of pokeweed (Phytolacca americana) and comfrey may result in additive effects. Although not well studied in humans, both herbs can precipitate human glycoproteins, agglutinate sheep red blood cells (SRBC), and stimulate lymphocyte adherence to nylon fibers.

  • Oral or absorbed comfrey, in combination with other pyrrolizidine alkaloid-containing herbs, may increase total levels of pyrrolizidine alkaloid consumed, which increases the risk for toxicity. Herbs containing pyrrolizidine alkaloids include alkanna, borage, butterbur, coltsfoot, forget-me-not, gravel root, hemp agrimony, hound's tongue, lungwort, and Senecio species.

  • Rosemary (Rosmarinus officinalis L.) or sassafras (Sassafras albidum Nutt.) extracts and comfrey extracts may both induce glutathione (GSH) adducts.

  • Comfrey may have uterine tonic effects. Other uterine tonic agents include chamomile (Matricaria chamomilla L.), pot marigold calendula (Calendula officinalis L.), cockscomb (Celosia cristata L.), plantain (Plantago lanceolata L. and Plantago major L.), shepherds purse (Capsella bursa pastoris L.), and St. John's wort (Hypericum perforatum L.).

Author Information

  • This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

References

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

  1. Altamirano JC, Gratz SR, Wolnik KA. Investigation of pyrrolizidine alkaloids and their N-oxides in commercial comfrey-containing products and botanical materials by liquid chromatography electrospray ionization mass spectrometry. J AOAC Int 2005;88(2):406-412. View Abstract

  2. Barbakadze VV, Kemertelidze EP, Targamadze IL, et al. [Novel biologically active polymer of 3-(3,4-dihydroxyphenyl)glyceric acid from two types of the comphrey Symphytum asperum and S. caucasicvum (Boraginoceae)]. Bioorg.Khim. 2002;28(4):362-366. View Abstract

  3. Barthomeuf CM, Debiton E, Barbakadze VV, et al. Evaluation of the dietetic and therapeutic potential of a high molecular weight hydroxycinnamate-derived polymer from Symphytum asperum Lepech. Regarding its antioxidant, antilipoperoxidant, antiinflammatory, and cytotoxic properties. J Agric.Food Chem 2001;49(8):3942-3946. View Abstract

  4. Dasgupta A. Review of abnormal laboratory test results and toxic effects due to use of herbal medicines. Am J Clin Pathol 2003;120(1):127-137. View Abstract

  5. Di Mambro VM, Fonseca MJ. Assays of physical stability and antioxidant activity of a topical formulation added with different plant extracts. J Pharm Biomed Anal. 2-23-2005;37(2):287-295. View Abstract

  6. Gray DE, Porter A, O'Neill T, et al. A rapid cleanup method for the isolation and concentration of pyrrolizidine alkaloids in comfrey root. J AOAC Int 2004;87(5):1049-1057. View Abstract

  7. Karavaev VA, Solntsev MK, Iurina TP, et al. [Antifungal activity of aqueous extracts from the leaf of cowparsnip and comfrey]. Izv.Akad.Nauk Ser.Biol 2001;(4):435-441. View Abstract

  8. 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. View Abstract

  9. Kucera M, Barna M, Horacek O, et al. Topical symphytum herb concentrate cream against myalgia: a randomized controlled double-blind clinical study. Adv Ther 2005;22(6):681-692. View Abstract

  10. Kucera M, Barna M, Horacek O, et al. 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. View Abstract

  11. Mei N, Guo L, Fu PP, et al. Mutagenicity of comfrey (Symphytum Officinale) in rat liver. Br J Cancer 3-14-2005;92(5):873-875. View Abstract

  12. Oberlies NH, Kim NC, Brine DR, et al. Analysis of herbal teas made from the leaves of comfrey (Symphytum officinale): reduction of N-oxides results in order of magnitude increases in the measurable concentration of pyrrolizidine alkaloids. Public Health Nutr 2004;7(7):919-924. View Abstract

  13. Predel HG, Giannetti B, Koll R, et al. 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. View Abstract

  14. Schaneberg BT, Molyneux RJ, Khan IA. Evaporative light scattering detection of pyrrolizidine alkaloids. Phytochem.Anal. 2004;15(1):36-39. View Abstract

  15. Thornfeldt C. Cosmeceuticals containing herbs: fact, fiction, and future. Dermatol Surg. 2005;31(7 Pt 2):873-880. View Abstract

Copyright © 2013 Natural Standard (www.naturalstandard.com)

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

Updated:  

March 22, 2017