Comfrey – a great herb for bruises, sprains and more

Comfrey is a plant that has been used medicinally for hundreds of years. The variety of names Comfrey is known by – Knitbone, Boneset, Bruisewort – reflect it’s healing properties.  The Greek physician Dioscorides and Roman author Pliny the Elder, both advocated for its benefits in healing broken bones, and in the Middle Ages it was a famous remedy for these. The name Comfrey is a corruption of con firma, alluding to its facilitatory effect on the uniting of bones. The botanical name, Symphytum, is derived from the Greek sympho, meaning ‘to unite’(1).

Other traditional uses for comfrey included for rheumatism and painful joints, bronchial conditions and gastrointestinal disorders such as gastritis and peptic ulcers. It has strongly mucilaginous and thus demulcent and expectorant properties due to its abundant content of fructans and other polysaccharides. It also contains rosmarinic acid and a heterocyclic organic compound called allantoin, which promotes granulation and tissue regeneration and is now an ingredient in many cosmetic products(2, 3). Interestingly, allantoin is also one of many compounds secreted from the roots of plants as a signalling chemical that conveys information on local conditions to other nearby plants(4).

The internal usage of comfrey is now somewhat controversial due to its content of pyrrolizidine alkaloids (PA’s), and most uses are now in the form of topical rather than internal dosage forms. Poultices, pastes, ointments and creams are used as anti-inflammatories in joint inflammations, arthritic swellings, sprains, bruises, contusions, haematomas, phlebitis, mastitis, glandular swellings as well as for the treatment of eczema, psoriasis, ulcers, and poorly healing wounds(5, 6).

Anti-inflammatory

Comfrey contains several compounds with anti-inflammatory effects, and various studies have shown comfrey to have anti-inflammatory properties(7-12).  Phenolic compounds such as globoidnan, rubdoisiin and rosmarinic acid isolated from comfrey roots have antioxidant and anti-inflammatory actions, including inhibiting release of cytokines such as interleukin (IL)-1β, IL-8 and tumor necrosis factor(9-11).

A hydroalcoholic extract of comfrey root reduced development of a pro-inflammatory scenario in primary human endothelial cells, in a dose-dependent manner. Effects included inhibition of interleukin-1 (IL-1) induced expression of pro-inflammatory markers including E-selectin, vascular cell adhesion molecule 1 (VCAM1), intercellular adhesion molecule 1 (ICAM1), and cyclooxygenase-2 (COX-2)(12). Activation of nuclear factor kappa-B (NF-κB), a transcription factor of central importance for the expression of these and other pro-inflammatory genes, was also inhibited(9, 12).

Clinical trials

The topical use of comfrey as an anti-inflammatory and analgesic has now been strongly substantiated by a range of clinical trials over the past 15 years.

The first of these was in 2004, when German researchers undertook a randomised trial involving application of comfrey ointment or a placebo ointment four times daily following acute ankle sprains incurred largely as a result of sporting activity. A more rapid reduction in swelling and pain upon movement, as well as improved joint mobility, occurred following comfrey ointment application over an eight day period (13).

A further trial by the same team which compared comfrey ointment with diclofenac gel, a popular drug treatment for acute ankle sprain, , also found favourable effects(14). A total of 160 patients were included in the randomised study, which was “investigator blind” rather than double-blind, due to the differences in appearance and smell for the comfrey ointment when compared to the diclofenac gel. Patients applied either comfrey or diclofenac four times daily over a seven day period. Treated skin areas were cleaned from every trace of the applied treatment before each patient was seen by the investigator however, making it impossible for the treatment agent to be identified.  As with the earlier trial, patients presented with uncomplicated, acute ankle sprains that had occurred within the previous six hours.

Both treatments showed a potent effect in reducing the tenderness reaction, but patients treated with comfrey experienced less pain. This was shown by a statistically significant greater AUC (Area Under the Curve) of a graph of the pressure required to cause pain, than that measured in the diclofenac group (p=0.046). After 7 days treatment an overall good or excellent efficacy was recorded by physicians for 78% of patients in the comfrey group compared to 61% in the diclofenac group, while the efficacy reported by patients themselves was 84.2% in the comfrey group, compared to 70.8% in the diclofenac group. Both physician and patient assessments of these differences reached statistical significance. This study provided further validation of the clinical efficacy of comfrey ointment in the treatment of acute sprains as a result of sports injuries, and furthermore implied superior efficacy to what is still one of the most popular drug treatments for such conditions(15).

Another trial compared comfrey ointment to placebo in 120 patients with a mean age of 37, suffering from acute upper or lower back pain. Significant improvements were measured in all outcome measurements, and a rapid onset of action reported (16). Similar benefits were reported in atrial involving a combination of comfrey root extract with methyl nicotinate (17).

Apart from these types of acute injuries, painful and chronic osteoarthritis of the knee, also responded to topical comfrey treatment in a randomised, double-blind, placebo-controlled clinical trial involving 220 patients. Reduced pain, an improvement in knee mobility, and an increase in quality of life, occurred over the three week treatment period. Improvements became more apparent with the duration of comfrey treatment, and adverse events were reported in 7 of the comfrey group, compared with 15 in the placebo group(18).

Muscle pain (myalgia), has also responded to treatment with a cream made from comfrey leaf, in a randomised, double-blind and controlled multicentre study involving 215 patients with muscle pain upon motion(19). Patients who received treatment with a cream containing the equivalent of 25 grams of fresh comfrey herb per 100 grams, experienced much less pain on active motion, pain at rest, and pain on palpation, than in those treated with the reference product which contained only 2.5 grams of fresh comfrey herb per 100 grams.

Reduction in scar formation?

Apart from its benefits in broken bones, bruises and sprains, another traditional applications for which comfrey products are said to be useful, is to facilitate wound healing and reduce scar formation. Research by Brazilian pharmacists reported wound healing properties by various comfrey leaf extract topical formulations, accompanied by a dramatic increase in collagen deposition and reduction in cellular inflammation(20).

Results from a recent German study, provide further support for these applications(21). This used an established in vitro model of human skin cells with the typical strata, for the observation of effects of applied substances on skin regeneration. Damage corresponding to a typical abrasion was created on day 1 by punching an opening into the epidermal fine structure down to the stratum basale, then samples were either untreated (controls) or exposed to comfrey cream on days 2, 3, 5, and 6. Light and electron microscopy then confirmed that application of comfrey cream led to a quicker regeneration of skin cells and to an earlier differentiation of cells towards a normal fine and layered structure. These effects were apparent within 4-7 days.

Comfrey has relatively mild antimicrobial properties compared with many other herbs however, and so should ideally only be applied to abrasions or wounds to help reduce scarring after they have initially healed.

Safety concerns

The ingestion of high doses of certain types of pyrrolizidine alkaloids, such as those found in ragwort and comfrey, has been associated with veno-occlusive disease of the liver, particularly when these are taken over a prolonged period of time. Over the years a small number of cases of human toxicity have been reported, mostly following ingestion of large doses of comfrey over a prolonged period of time(22, 23, 24). This appears to relate to formation of highly reactive compounds during pyrrolizidine alkaloid metabolism in the liver. Comfrey roots contain the highest levels of pyrrolizidine alkaloids, and young leaves contain higher levels than more mature leaves.

While previously comfrey had been used for hundreds of years without reported problems, because of this, it is now generally recommended that the medicinal use is restricted to topical use only, although short term internal use is still sometimes recommended by herbal practitioners. Products containing less than certain levels of pyrrolizidine alkaloids, are also able to be taken internally in Germany and other European countries, without restrictions on the duration of treatment. Internal use of all types of comfrey should however be avoided by those with hepatic disorders, or those taking potentially hepatotoxic medications.   

These safety concerns have recently been rebuttled, however, by at least three separate studies. A German study in which comfrey was fed to chickens as 4% of their diet for 32 days from when they were one day old, revealed no signs of impairment of liver function, mineral homeostasis, bone mineral density or intestinal microanatomy. Pyrrolizidine alkaloid levels were also below the detection limit in liver and breast muscle(25)

Limits placed by some regulatory agencies on pyrrolizidine alkaloid content in topical preparations, have been shown to be an overestimation of any risk (26).  A collection of Australian medical herbalists have alsorecently reviewed this subject, and challenged the evidence base for case reports of safety concerns involving comfrey and its content of unsaturated pyrrolizidine alkaloids(24).

Finally

Aches and pains, sprains and strains, have always afflicted humans just as they have other animals. Taken together with inflammatory joint and muscle conditions which become more common with aging, its hardly surprising that there are multiple drug-based medicines produced to give relief to these painful problems. The fact that various preparations of a common and easily grown plant with thousands of years of history of helping with these types of ailments has had its efficacy validated by several well designed human clinical trials, highlights an impressive natural alternative.

References: 

  1. Grieve M, A Modern Herbal, 1931. Ed CF Leyel, Cape, London.
  2. Thornfeldt C. Cosmeceuticals containing herbs: fact, fiction, and future. Dermatol Surg. 2005 Jul;31(7 Pt 2):873-80; discussion 880. doi: 10.1111/j.1524-4725.2005.31734. PMID: 16029681.
  3. Buszewska-Forajta M, Siluk D, Daghir-Wojtkowiak E, Sejda A, Staśkowiak D, Biernat W, Kaliszan R. Studies of the effect of grasshopper abdominal secretion on wound healing with the use of murine model. J Ethnopharmacol. 2015 Dec 24;176:413-23. doi: 10.1016/j.jep.2015.11.004. Epub 2015 Nov 6. PMID: 26549269.
  4. Wang NQ, Kong CH, Wang P, Meiners SJ. Root exudate signals in plant-plant interactions. Plant Cell Environ. 2021 Apr;44(4):1044-1058. doi: 10.1111/pce.13892. Epub 2020 Oct 7. PMID: 32931018.
  5. Wichtl M, Herbal Drugs and Phytopharmaceuticals. Ed Norman Grainger Bisset, Medpharm Scientific Publishers, CRC Press, Stuttgart, 1994.
  6. Potters Herbal Cyclopaedia, Wren RC. Williamson EM. CW Daniel Co Ltd, Saffron Walden, UK, 2003.
  7. Andres R, Brenneisen R, Clerc JT. Relating antiphlogistic efficacy of dermatics containing extracts of Symphytum officinale to chemical profiles. Planta Medica, 1989; 55:643-644.
  8. Hiermann A, Writzel M. 1988. Antiphlogistic glycopeptide from the roots of Symphytum officinale. Pharm Pharmacol Lett 8:154-157.
  9. Trifan A, Opitz SEW, Josuran R, Grubelnik A, Esslinger N, Peter S, Bräm S, Meier N, Wolfram E. Is comfrey root more than toxic pyrrolizidine alkaloids? Salvianolic acids among antioxidant polyphenols in comfrey (Symphytum officinale L.) roots. Food Chem Toxicol. 2018 Feb;112:178-187. doi: 10.1016/j.fct.2017.12.051. Epub 2017 Dec 28. PMID: 29288756.
  10. Trifan A, Wolfram E, Esslinger N, Grubelnik A, Skalicka-Woźniak K, Minceva M, Luca SV. Globoidnan A, rabdosiin and globoidnan B as new phenolic markers in European-sourced comfrey (Symphytum officinale L.) root samples. Phytochem Anal. 2021 Jul;32(4):482-494. doi: 10.1002/pca.2996. Epub 2020 Oct 5. PMID: 33015885.
  11. Trifan A, Skalicka-Woźniak K, Granica S, Czerwińska ME, Kruk A, Marcourt L, Wolfender JL, Wolfram E, Esslinger N, Grubelnik A, Luca SV. Symphytum officinale L.: Liquid-liquid chromatography isolation of caffeic acid oligomers and evaluation of their influence on pro-inflammatory cytokine release in LPS-stimulated neutrophils. J Ethnopharmacol. 2020 Nov 15;262:113169. doi: 10.1016/j.jep.2020.113169. Epub 2020 Jul 31. PMID: 32739565.
  12. Seigner J, Junker-Samek M, Plaza A, D’Urso G, Masullo M, Piacente S, Holper-Schichl YM, de Martin R. A Symphytum officinale Root Extract Exerts Anti-inflammatory Properties by Affecting Two Distinct Steps of NF-κB Signaling. Front Pharmacol. 2019 Apr 26;10:289. doi: 10.3389/fphar.2019.00289. PMID: 31105555; PMCID: PMC6498879.
  13. Koll R, Buhr M, Dieter R, Pabst H, Predel HG, Petrowicz O, Giannetti B, Klingenburg S, Staiger C. 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 Sep;11(6):470-7. doi: 10.1016/j.phymed.2004.02.001. PMID: 15500257.
  14. 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 Nov;12(10):707-14. doi: 10.1016/j.phymed.2005.06.001. PMID: 16323288.
  15. D’Anchise R, Bulitta M, Giannetti B. Comfrey extract ointment in comparison to diclofenac gel in the treatment of acute unilateral ankle sprains (distortions). Arzneimittelforschung. 2007;57(11):712-6. doi: 10.1055/s-0031-1296672. PMID: 18193693.
  16. 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 Jul;44(9):637-41. doi: 10.1136/bjsm.2009.058677. Epub 2009 May 21. PMID: 19460762.
  17. Pabst H, Schaefer A, Staiger C, Junker-Samek M, Predel HG. Combination of comfrey root extract plus methyl nicotinate in patients with conditions of acute upper or low back pain: a multicentre randomised controlled trial. Phytother Res. 2013 Jun;27(6):811-7. doi: 10.1002/ptr.4790. Epub 2012 Aug 8. PMID: 22887778; PMCID: PMC3747459.
  18. 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 Jan;14(1):2-10. doi: 10.1016/j.phymed.2006.11.006. Epub 2006 Dec 13. PMID: 17169543.
  19. 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 Nov-Dec;22(6):681-92. doi: 10.1007/BF02849961. PMID: 16510384.
  20. Araújo LU, Reis PG, Barbosa LC, Saúde-Guimarães DA, Grabe-Guimarães A, Mosqueira VC, Carneiro CM, Silva-Barcellos NM. In vivo wound healing effects of Symphytum officinale L. leaves extract in different topical formulations. Pharmazie. 2012 Apr;67(4):355-60. PMID: 22570943.
  21. Dähnhardt D, Dähnhardt-Pfeiffer S, Groeber-Becker F, Fölster-Holst R, Schmidt M. Epidermal Regeneration Induced by Comfrey Extract: A Study by Light and Electron Microscopy. Skin Pharmacol Physiol. 2020;33(4):189-197. doi: 10.1159/000509121. Epub 2020 Jul 17. PMID: 32683369.
  22. Awang DVC, Comfrey. Revue Pharmaceutique Canadienne, 1987; Feb. 101-104.
  23. Mei N et al, Metabolism, genotoxicity, and cardinogenicity of Comfrey. J Toxicol and Environmental Health, Part B, 2010:13, 509-526. ISSN: 1093-7404.
  24. Avila C, Breakspear I, Hawrelak J, Salmond S, Evans S. A systematic review and quality assessment of case reports of adverse events for borage (Borago officinalis), coltsfoot (Tussilago farfara) and comfrey (Symphytum officinale). Fitoterapia. 2020 Apr;142:104519. doi: 10.1016/j.fitote.2020.104519. Epub 2020 Feb 24. PMID: 32105669.
  25. Oster M, Reyer H, Keiler J, Ball E, Mulvenna C, Muráni E, Ponsuksili S, Wimmers K. Comfrey (Symphytum spp.) as an alternative field crop contributing to closed agricultural cycles in chicken feeding. Sci Total Environ. 2020 Nov 10;742:140490. doi: 10.1016/j.scitotenv.2020.140490. Epub 2020 Jun 27. PMID: 32634689.
  26. Kuchta K, Schmidt M. Safety of medicinal comfrey cream preparations (Symphytum officinale s.l.): The pyrrolizidine alkaloid lycopsamine is poorly absorbed through human skin. Regul Toxicol Pharmacol. 2020 Dec;118:104784. doi: 10.1016/j.yrtph.2020.104784. Epub 2020 Sep 15. PMID: 32941922.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s