Symphytum officinalis L. / Smeerwortel

Algemene en Botanische Informatie

Namen: Consoude (Fr.), Beinwell (D.), Comfrey (E.)
Etymologie: Smeerwortel = wortel met smeer (slijm), wortel om smeer­seltjes te maken. Consolida = consolideren, bevestigen. Zie ook In de naam van... Smeerwortel | Kunst en cultuur: Taal 

Andere namen
boneset (Source: Hortus 3 ) – English
comfrey (Source: Food Feed Crops US ) – English
common comfrey (Source: World Econ Pl ) – English
consound (Source: Dict Rehm ) – English
healing-herb (Source: Hortus 3 ) – English
knitbone (Source: Pulmonaria ) – English
slippery-root (Source: Pulmonaria ) – English
consoude officinale (Source: Dict Rehm ) – French
grande consoude (Source: Dict Rehm ) – French
Beinwell (Source: Dict Rehm ) – German
echter beinwell (Source: Pulmonaria ) – German
consolda maggiore (Source: F Ital ) – Italian
consolda-maior (Source: Dict Rehm ) – Portuguese



Soorten:
Symph. officinale ssp. officinale, ssp. uliginosum (A. KERNER) NYAN,
Symph. asperum Lepechin,
Symph. x uplandicum NYMAN: bastaard van S. asperum en S. officinale,

Verwanten:
  • Cynoglossum off. - Echte hondstong,
  • Anchussa off. - Ossetong,
  • Borago off. - Bernagie, Komkommerkruid
  • Lithospermum off. - Glad parelzaad,
  • Pulmonaria off. - Gevlekt longkruid.
Ecologie: Vaste plant vooral groeiend op vochtige, voedselrijke plaat­sen langs beken.

Materia Medica, gebruikte delen

Consolidae radix / Symphyti radix, De wortel van Symphytum officinale L. soms ook het blad vooral vers als kompres

Oogst:
In het voor- en najaar de wortel.
In de zomer het blad van Symphytum uplandicum e.a. als voeder­plant.
Drogen: In de lengte doorsnijden, met kunstmatige warmte, 40°drogen.

Beschrijving:
Wortelstukken aan de buitenkant zwart tot zwartbruin, aan de binnenkant melkwit tot lichtbruin.
Smaak: slijmerig, wat zoet en zwak samentrekkend.
Import: Uit Bulgarije, Polen, Roemenië en Hongarije.

Samenstelling, inhoudsfoffen

** Slijmstoffen 29 % vooral bestaande uit fructose
** Allantoïne 0,7 % = purinederivaat (3) vooral aanwezig van januari tot maart
** Pyrrolizidine-alkaloïden: o.a. consolidine 0,02-0,07 %
* Looistoffen 4-6 %
* Aminozuren o.a. asparagine tot 3 %
* Chlorogeen- en koffiezuur, rozemarijnzuur.
* Lithospermzuur
* Gommen, harsen en wat inuline

Farmacologie, fysiologische werking

** Wondgenezend
- Allantoïne bevordert weefselherstel (granulatie)
- Looi- en slijmstoffen
- Stimulerend op epitheel
* Bevordert de callusvorming
* Adstringentium (looistoffen)
* Ontstekingswerend (gewrichten)
Pyrrolizidine-alkaloïden kunnen hepatotoxisch en cancerogeen werken. 1 kopje thee kan ± 8 mg alkaloïden bevatten.

Indicatie, medisch gebruik van Symphytum

Huid en Slijmvliezen
** Alle verwondingen
- Ook brandwonden (pijnstillend) vers gekneusd bladkompres
- Chronische, etterende wonden.

** Beenderbreuken
* Hematomen, kneuzingen, blauwe plekken. Zie ook Arnica
* Andere huidproblemen:
            tepelkloven. Vers compres
            ulcus cruris 'open been'
            psoriasis Zie R./ blad, kompres
* Ulcus ventriculi (maagzweer), gastritis. Beter Calendula, Matricaria., Glycyrhiza
* Stomatitis, faryngitis
* Paradontose

Gewrichten / Beenderstelsel / Uitwendig als kompres, zalf.
* Gewrichtsontsteking. Zie reumaplanten
* Tenniselleboog (epicondylitis)
* Voetbalknie

Receptuur en bereidingswijzen

Uitwendig: Kompres van vers gekneusd blad of fijn ­gemaakte wortel
Inwendig:
- Mac. rad. 10 u, 100 g/1 l (Valnet)
- Inf. rad. 15', 5-10 g/kop
Dos.: 3 x daags gedurende 3 weken (Wichtl, Willuhn)

Tinctuur 1:5
Nota: Koken kan de slijm- en looistoffen veranderen (Van Hel­lemont)
Fytofarmaca: Veel preparaten vooral als analgetica, anti-reumatica en antiflogistica

Species: R./
Symphyti vloeib. extr. 12 g (Leclerc)
Bergamot e.o. 20 dr.
Zinkoxyde 20 g
Lanoline 10 g
Vaseline 30 g                   Ind.: spataderen

R./
Urtica hb. 100 g                         (Moatti)
Saponariae rad. 150 g                 Ber.: dec. 10', 2 l water.
Symphyti rad. 200 g                   Gebr.: volbad 32 C, duur 20', 1 x daags gedurende 1 week.
                                               Ind.: psoriasis

In de keuken (volwassen blad, met mate)

* het blad gestoofd samen met spinazie
* bij de soep
* gefrituurd, tempura als bijgerecht

Geschiedenis en Wetenschappelijk Onderzoek

In de Oudheid reeds bekend als bloedstelpend, wondgenezend en tegen botbreu­ken.
Heschtetterus: Sterke verhalen over de werking van Symphitum o.a. over het terugkrijgen van de maagdelijkheid door het baden in een aftreksel van Symphytum. Rararum observatianum medicinalium decades tres. Decas III, Casus V - 1624.
Fuchsius: «De Waelwortel is matelijk koud van aard / ende droog in den tweede graad / dik makende / ende de scherpigheid der vochtigheden verzachtende van krachten. ... Voor scheursels der jonge kinderen». (Vochtige meelpap van de wortel)
Ravelingius: «Voor pijn van 't Flerecijn». (kompres vers geraspte wortel)
Dodonaeus: «Voor Bloedspuwen, overtollige maandstonden, zweringen van longen en nieren».
Leclerc: ' j'ai pu, en 1915, apprécier les services que me rendit l'application locale de pulpe fraiche de racine pour panser des brulures et des fongosités de mauvaise nature empechaient la cicatrisation'

Referenties
  • Macalister C.: A new cell proliferant.
  • Bramwell W.: The new cell proliferant. Ervaringen met genezing en herstel van maagzwe­ren. British Medical Journal - 06.01.1912.
  • Titherley, Coppin: Isoleerden het allantoïne.
  • Leclerc H., Decaux F.: Emploi de la Grande Consoude dans les ulcères variqueux. Journ. des Practiciens - 24.04.1943.
  • Teissier J.L.: Une plante épithéliogène: La Grande Consoude. "... le retard ou l'absence­ d'épider­misation". Etude botanique, pharmacolo­gique et thérapeutique. Thèse de Paris - 1947.
  • Röder E.: Dtsch. Apoth. Ztg. 122/2081 - 1982.
  • Stengel P. e.a.: Dtsch. Apoth. Ztg. 122/851 - 1982.
  • Schoental R.: Toxicol. Letters 10/323 - 1982.
  • Roitman J.N.: Onderzoek naar het gehalte aan alkaloïden in waterig aftreksel. Lancet 1, 8226/944 - 1981; C.A. 95/92071 - 1981.
Andere onderzoeken
  • Goldman R.S. e.a.: Het bladextract had wondge­nezende eigenschappen en een licht pijnstillende werking bij ratten. Fitoterapia 56/323 - 1985.
  • Gracza, L., H. Koch, et al. (1090). Biochemical-pharmacological investigations of medicinal agents of plant origin: Isolation of rosmarinic acid from Symphytum officinale and its anti-inflammatory activity in an in-vitro model. Archiv Der Pharmazie 318(12): 1090-1095.
  • Hiermann, A. and M. Writzel (1998). Antiphlogistic glycopeptide from the roots of Symphytum officinale. Pharmaceutical and Pharmacological Letters. Dec. 8(4): 154-157. {a} Institute of Pharmacognosy, University of Graz, Universitaetsplatz 4, A-8010, Graz, Austria
  • Hirosaki K. e.a., Japan: Onderzoek naar de anti-tumorale werking van het extract en het effect bij levercyrrhose. Patent 78/88312 - 03.08.1978; C.A. 89/186068 - 1978.
  • Valavichyusk, Y. M., K. K. Yankyavichyus, et al. (1989). Antitumor activity of medicinal plants in the Lithuanian SSR (USSR): 9. Garden angelica, common comfrey, marsh violet, wonder violet, and cowberry. Lietuvos Tsr Mokslu Akademijos Darbai Serija C Biologijos Mokslai(3): 146-151.
Algemene literatuur en doc. Maurice Godefridi
  • Lawrence D. Hills: Comfrey, past, present and future.
  • Terruso Wilkes - Medical Attributes of Symphytum officinale - Comfrey (over PA) - 1999
  • Van den Dungen F.M.: Smeerwortel: geneeskracht, fictie of realiteit? Nederlands Tijdschrift voor Fytotherapie 3 - 1994.
  • Leclerc H.: Une panacée medico-chirurgicale: la Grande Consoude. Bull. de la Soc. d'Histoire de la Pharmacie - 1921.
Internetlinks
Pubmed links
  • 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 Pubmed 
  • Englert K., Mayer J.G., Staiger C. Symphytum officinale L. Zeitschrift für Phytotherapie, 2005, 26, 158–168
  • Giannetti B.M., Staiger C., Bulitta M., Predel H.G. 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), 637-41 Pubmed 
  • 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 Pubmed 
  • Györik S., Stricker H. Severe pulmonary hypertension possibly due to pyrrolizidine alkaloids in polyphytotherapy. Swiss Med Wkly, 2009, 139(13-14), 210-1 Pubmed 
  • Hänsel R., Sticher O., Steinegger E. Pharmakognosie - Phytopharmazie. Berlin, Heidelberg: Springer, 1999
  • Koll R., Buhr M., Dieter R., Pabst H., Predel H.G., 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, 11(6), 470-7 Pubmed 
  • Kommission E Monographien
  • 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), 681-92 Pubmed 
  • Lin C.C. et al. An outbreak of foxglove leaf poisoning. J Chin Med Assoc, 2010, 73(2), 97-100 Pubmed 
  • Predel H.G., 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), 707-14 Pubmed 
  • Staiger C. Comfrey: ancient and modern uses. Pharm J, 2007, 279, 732
  • Stickel F., Seitz H.K. The efficacy and safety of comfrey. Public Health Nutr, 2000, 3(4A), 501-8 Pubmed 


For centuries, comfrey has been used as a traditional medicinal plant for the treatment of painful muscle and joint complaints (Kothmann, 2003; Englert et al., 2005). Commonly found throughout Europe and parts of Asia, the plant also naturalized in North America, where it rapidly spread. Native Americans also recognized its healing powers and included comfrey in their therapeutic armamentarium (Hamel and Chiltoskey, 1975; Stammel, 1986). Comfrey has also been used in veterinary medicine (Rabinovich, 1981).

The German Commission E has assessed preparations containing Symphytum officinale L. positively for the treatment of blunt injuries (Kommission E, 1990a, 1990b). A European Scientific Cooperative on Phytotherapy Monograph is available for comfrey root (Symphyti radix; ESCOP, 2009). In addition, comfrey is described in the Hager Monographs (Staiger, 2009).

The constituents of comfrey root include 0.6–4.7% allantoin (Dennis et al., 1987); abundant mucilage polysaccharides (about 29%) composed of fructose and glucose units (Franz, 1969); phenolic acids such as rosmarinic acid (up to 0.2%), chlorogenic acid (0.012%) as well as caffeic acid (0.004%) and α-hydroxy caffeic acid (Andres, 1991; Grabias and Swiatek, 1998; Teuscher et al., 2009); glycopeptides and amino acids (Hiermann and Writzel, 1998); and triterpene saponins in the form of monodesmosidic and bidesmosidic glycosides based on the aglycones hederagenin (e.g. symphytoxide A), oleanolic acid (Aftab et al., 1996) and lithospermic acid (Wagner et al., 1970).

Comfrey root also consists of pyrrolizidine alkaloids with 1,2-unsaturated necine ring structures, almost entirely in the form of their N-oxides, the main ones being 7-acetylintermedine and 7-acetyllycopsamine together with smaller amounts of intermedine, lycopsamine and symphytine (Brauchli et al., 1982). The total amount of pyrrolizidine alkaloids given by different authors varies from 0.013% to 1.2% based on the analytical methods used (Tittel et al., 1979; Brauchli et al., 1982; Neidhardt, 1982; Stengl et al., 1982; Gracza et al., 1985; Vollmer et al., 1987; Mütterlein and Arnold, 1993).

The pyrrolizidine alkaloids echimidine and symlandine are not found in S. officinale L. and can be used as indicators of possible adulteration with other Symphytum species, such as S. × uplandicum or S. asperum (Mütterlein and Arnold, 1993). Nowadays, only pyrrolizidine-depleted or pyrrolizidine-free extracts are used in proprietary medicinal products. Special cultivars are also used (Schmidt, 2008).

The therapeutic properties of comfrey are based on its antiinflammatory and analgesic effects. Comfrey also stimulates granulation and tissue regeneration, and supports callus formation (Kommission E, 1990a, 1990b). However, the key activity-determining constituents of comfrey extracts and its molecular mechanisms of action have not been completely elucidated. Allantoin and rosmarinic acid are probably of central importance to its pharmacodynamic effects (Andres et al., 1989). No clinical-pharmacokinetic investigation results in humans have been published so far on the absorption, distribution and elimination of the constituents of comfrey extracts.




Recent onderzoek: Symphytum / Smeerwortel tegen kneuzingen
Anwendung und Verträglichkeit von Beinwellcreme (Symphyti herba) bei Kindern mit akuten stumpfen Traumen. Z Phytother 2010; 31(1): 61-66. Smeerwortel uitwendig tegen kneuzingen en blauwe plekken.
Die therapeutische Anwendbarkeit und Anwendungssicherheit einer topischen Cremezubereitung aus den oberirdischen Pflanzenteilen des Beinwellkultivars »Symphytum × uplandicum Nyman ‚Harras'« zur pädiatrischen Therapie akuter stumpfer Traumen (Prellungen, Zerrungen, Verstauchungen) wurde in einer offenen Anwendungsstudie an 196 Kindern im Alter von 4-12 Jahren geprüft. Das in dieser Studie gefundene Ausmaß an Symptomverbesserungen (Druckschmerz, Bewegungsschmerz, funktionelle Behinderung, Schwellung und Hämatome) lag für die einzelnen Parameter im Bereich von 84,5-100% (p < 0,001), bei gleichzeitig ausgezeichneter Verträglichkeit und Compliance. Topische Beinwellcreme bestätigt sich damit als ein Mittel der Wahl für die Behandlung akuter stumpfer Verletzungen bei Kindern.

Summary: Application and safety of comfrey cream (Symphyti herba) in paediatric treatment of acute blunt traumata
In an open observational study the therapeutic applicability and safety of application of a topical cream preparation from the aerial plant parts of the comfrey cultivar “Symphytum × uplandicum Nyman ‘Harras'” was tested in 196 children in the age of 4 to 12 years with respect to the paediatric treatment of acute blunt traumata (contusions, strains and distortions). The extent of symptom improvement observed in this study (pain on palpitation, pain in motion, functional impairment, oedema and haematoma) was found in the range of 84.5 to 100% for the single parameters (p < 0.001) with at the same time an excellent tolerability and compliance. Topical comfrey cream was therefore confirmed as a remedy of choice for the treatment of acute blunt traumata in children.

Comfrey root has been used for centuries in the treatment of wounds and sprains and strains (1). Yet, in spite of common usage, Medline did not index a clinical trial relating to comfrey until 2002 (2) . Since then 5 additional trials have been published which provide valuable evidence relating to safety and effectiveness for several conditions which are common in chiropractic practice (3-7) .
Possibly the greatest obstacle to the wide spread use of comfrey is the concern over the presence of pyrrolizidine alkaloids (PA) in comfrey root which have demonstrated hepatotoxic, carcinogenic and mutagenic properties in oral preparations (8). For this reason only topical preparations are considered safe. A recent study demonstrated a PA free form, Kytta-Salbe f, did not result in a mutagenic effect (8).

Back Pain: The effectiveness of comfrey root extract was recently demonstrated in a double blind randomized clinical trial (RCT) with 120 subjects over 5 days for acute upper and lower back pain. The primary outcome measure was the visual analog scale (VAS) on active movement. Included in the secondary outcome measures were the VAS during rest. The treatment group experienced a 95.2% decrease in pain while the placebo group experienced a 37.8% decrease in pain. Dosage of comfrey root was 4 grams of ointment 3 times per day. The authors concluded the results were “clear cut and consistent” and reported improvement began within 1 hour of application (3)

Osteoarthritis: In 2007 another RCT investigated the effectiveness of comfrey root in the treatment of knee osteoarthritis over 3 weeks. This study enrolled 220 subjects with an average age of 57.9 years. Dosage in this trial was 2 grams 3 times per day. In this study the VAS dropped 54.7% in the treatment group and 10.7% in the placebo group. Statistical significance was achieved (p<.001). Additionally statistically significant improvements were noted in quality of life, mobility, and physician and patient assessment. There were no adverse reactions reported (4).

Ankle Sprain: Three separate studies have demonstrated the effectiveness of comfrey root in the treatment of acute ankle sprains. In one observational study 492 questionnaires were returned from patients with ankle sprains and their physicians. Overall 45-47% improvement in pain and tenderness was observed (2). Two other RCTs with 162 and 142 patients respectively found comfrey root to be superior to the placebo in 1 study (5) and equal in effectiveness to Diclofenic gel in the other (7). Of interest in the Diclofenac study was the author observation that comfrey root may actually be superior based on primary and secondary variables. 

References
1. Mills SY. Out of the Earth: The Essential Book of Herbal Medicine. New York: Viking; 1991.
2. Koll R, Klingenburg S. [Therapeutic characteristance and tolerance of topical comfrey preparations. Results of an observational study of patients]. Fortschr Med Orig 2002;120(1):1-9.
3. 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.
4. Grube B, Grunwald 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.
5. Koll R, Buhr M, Dieter R, Pabst H, Predel HG, Petrowicz O, 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 Sep;11(6):470-7.
6. Kucera M, Barna M, Horacek O, Kalal J, Kucera A, Hladikova M. Topical symphytum herb concentrate cream against myalgia: a randomized controlled double-blind clinical study. Adv Ther 2005 Nov;22(6):681-92.
7. Predel HG. 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. 2005 Nov. 



Comfrey Root Ointment Reduces Pain in Patients with Knee Osteoarthritis 
HerbalGram. 2007; 76:25-26 American Botanical Council
Reviewed: Grube B, Grunwald 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. Phytomed. 2007;14(1):2-10.

Rheumatic disorders have different causes (inflammatory, infectious, degenerative, metabolic) and are located at different parts of the body(joints, tendons, muscles, spine). The multitude of diseases and complaints is matched by an equally large number of therapeutic treatment options. Phytomedicines such as ointments applied topically have the benefit of being applied on target and have fewer or no adverse drug reactions compared to conventional pharmaceutical medications taken orally.
For many years, the leaves and roots of the traditional medicinal plant comfrey (Symphytum officinale, Boraginaceae) have been used both internally and externally in different forms of administration for the treatment of a variety of diseases (e.g., bone fractures, wounds, ulcers). Recently, several clinical trials have proven the efficacy of comfrey in the treatment of distortions, strains and sprains, and other muscle and joint complaints.1,2,3,4 The pharmacodynamics of preparations made from the root may be attributable to the presence of allantoin, rosmarinic acid, and other hydroxycinamon acid derivatives, as well as mucopolysaccharides.

The goal of this randomized, placebo-controlled, double-blind study performed in Berlin, Germany, was to investigate the effect of daily application of a comfrey root extract (Kytta-Salbe®f, Merck Selbstmedikation GmbH, Darmstadt, Germany) over a 3-week period in patients suffering from painful osteoarthritis of the knee. Patients were randomly allocated to 1 of 2 treatment groups and received either Kytta-Salbe or placebo. The patients were to massage into the knee a 6 cm long thread of comfrey ointment or placebo 3 times per day.
Kytta Salbe contains comfrey root liquid extract (1:2, ethanol 60% V/V, 35%), and the extract specification allows an allantoin content of 0.2–0.5% (m/m). A special procedure removes more than 99% of the potentially hepatotoxic pyrrolizidine alkaloids contained in S. officinale (specification: < 0.35 ppm in the proprietary medicinal product). The German Commission E monograph on comfrey root approves it for external use as treatment for bruising, pulled muscles and ligaments, and sprains. Further, the daily dose of applied salve should not exceed an equivalent of more than 100 mcg pyrrolizidine alkaloids with 1,2-unsaturated necine structure, including its N-oxides.5

A total of 220 patients participated in the study. Pain relief was the primary criterion for evaluation. The results of the study demonstrated a greater decline in total pain in the comfrey group (54.7%) compared to the placebo group (10.7%). The average difference of 44.0% between the groups was significant (P<0.001). The decline in pain at rest and pain on movement was similar and statistically different in the comfrey root ointment group (P<0.001). The patients’ diaries confirmed the significance seen in the pain parameters.

The WOMAC (Western Ontario and McMaster Universities) total score (a secondary criterion measuring pain, stiffness, and function) also improved similar to the pain scores. At the end of the trial, a reduction by 58.0% was recorded for the comfrey group versus 14.1% for the placebo group. The average group difference of 43.9% was significant (P<0.001). Other exploratory parameters (quality of life, mobility of the knee, clinical global impression, and global assessment of efficacy) revealed a significant superiority (P<0.001, each) of the comfrey group over the placebo group.

The results of this study suggest that Kytta-Salbe comfrey root ointment is well suited for the treatment of osteoarthritis of the knee. Pain was reduced, mobility of the knee was improved, and quality of life was increased. The authors conclude that because the comfrey root ointment was significantly superior to the placebo medication with regard to all the parameters, this study proves the therapeutic efficacy of the comfrey root ointment in the treatment of painful osteoarthritis of the knee.

—Jennifer Minigh

References
  • Koll R, Buhr M, Dieter R, et al. Efficacy and tolerance of a comfrey root extract (Extr. Rad. Symphyti) in the treatment of ankle distortions: results of a multicenter, randomized, placebo-controlled, doubleblind study. Phytomedicine. 2004;11:470–477.
  • Predel HG, Giannetti B, Koll R, Bulitta M, Staiger C. Efficacy of a comfrey root extract ointment in comparison to diclofenac in the treatment of ankle distortions: results of an observer-blind, randomized, multicenter study. Phytomedicine. 2005;12:707–715.
  • Kucera M, Barna M, Horacek O, Kovarikova J, Kucera A. Topical symphytum herb concentrate cream against myalgia: a randomized controlled double blind clinical study. Adv Ther. 2005;22:681–692.
  • Staiger C. Beinwell – eine moderne Arzneipflanze [Comfrey – a modern herbal drug]. Z Phytother. 2005;26:169–173.
  • Blumenthal M, Busse WR, Goldberg A, Gruenwald J, Hall T, Riggins CW, Rister RS, eds. Klein S, Rister RS, trans. The Complete German Commission E Monographs Therapeutic Guide to Herbal Medicines. Austin, TX: American Botanical Council; Boston: Integrative Medicine Communications; 1998.


Chemical Constituents of Comfrey
There has been much research and study done (Australia, Great Britain, Africa, USSR, United States) on Prickly Comfrey (Symphytum asperrimum) and Quaker Comfrey (Symphytum peregrinum) as forage plants due to their high protein content and the fact that Comfrey is the only land plant that takes vitamin B12 from the soil. The entire plant is a good source of vegetable protein, and the green leaves contain vitamins A, C, E, and several B vitamins, including choline, the fat-emulsifying vitamin that helps fight cholesterol deposits. Other ingredients are folic acid, the anti-anemia vitamin, and some B12, which controls the deadly pernicious anemia. The leaves also contain the vital minerals of calcium, potassium, phosphorus, some iron, a little iodine, and many other trace minerals. Comfrey is one of the richest sources of silicon in the botanic world, surpassed only by horsetail grass. On the following pages is a list of the chemical constituents in Symphytum, their medicinal actions and where Symphytum lands on the list of plants species with the highest amount of that constituent (ppm = parts per million): 

allantoin (leaf) 13,000ppm; (root) 6,000-8,000 ppm-the biological activities are antidandruff, anti-inflammatory, anti-peptic, anti-psoriac, anti-ulcer, immuno-stimulant, keratolytic, sunscreen, suppurative, vulnerary. Symphytum is the number one plant species with the highest amount of allantoin. 

aluminum (root) 237 ppm-the biological activities are anti-silicotic, anti-vaginitic, candidicide, encephalopathic. Symphytum does not make the top plant list for this constituent. 

ascorbic-acid (root) 132 ppm-the list of the biological activities of this mineral is about 65 actions long! For my purposes, I would highlight the fact that it is anti-hepatotoxic, anti-inflammatory, anti-hemorrhagic, anti-mutagenic, anti-oxidant, anti-septic, anti-tumor, anti-ulcer, cancer-preventative, diuretic, interferonogenic, uricosuric, and vulnerary. Symphytum does not make the top plant list for this constituent. 

ash (root) 140,000 ppm-no biological activities reported. Symphytum does not make the top plant list for this constituent. 

asparagine (root) 10,000-30,000 ppm-the biological activities of this mineral are anti-sickling and diuretic. Symphytum is the third highest plant species with this mineral. 

beta-carotene (root) 660 ppm-again, the biological activity list is too long to mention, so I will highlight what I see as the most pertinent to this study: anti-carcinomic, anti-leukoplakic, anti-mutagenic, anti-oxidant, anti-tumor, anti-ulcer, cancer-preventative, immuno-stimulant, interferon-synergist, and phagocytotic. Symphytum is number fifteen on the top plant species list. 

bornesitol (root)-no amount is listed. There are no biological activities reported for this constituent. Symphytum is number three on the top plant species list. 

caffeic-acid (root)-no amount is listed. The biological activities that most pertain to Comfrey use are the following: analgesic, anti-bacterial, anti-cancer, anti-carcinogenic, anti-hepatotoxic, anti-inflammatory, anti-mutagenic, anti-oxidant, antiseptic, anti-spasmodic, anti-viral, cancer-preventative, diuretic, fungicide, hepatoprotective, immuno-stimulant, insectifuge, and sedative. Symphytum doesn't make the top plant list for this constituent. 

calcium (root) 11,300 ppm-this mineral is crucial to the formation of strong bones and teeth, proper blood clotting, cancer preventative, anti-atherosclerotic, among many other actions. Symphytum doesn't make the top plant list for this constituent. 

carbohydrates (root) 759,000 ppm-there are no biological activities reported, though, these are the building blocks of foods for the body. Symphytum doesn't make the top plant list for this constituent. 

carotenes (plant) 6,300 ppm-this is vitamin A and is intrinsically connected to beta-carotenes because one beta-carotene molecule can be converted to two carotenes in the body. Both of these substances are known as liver builders and cleansers. It is helpful in wound healing, anti-oxidant, protects mucous membranes, anti-cancer, and is known to be non-toxic in any amount. “Many researchers are now saying that people who have a high beta-carotene intake may have a lower risk of cancer.” Symphytum is number one on the plant species list to contain the highest amount of this vitamin. 

chlorogenic-acid (root)-amount is not listed. The biological activities that most pertain to the use of Comfrey are as follows: anti-bacterial, anti-cancer, anti-hepatotoxic, anti-inflammatory, anti-oxidant, antiseptic, anti-viral, cancer-preventative, diuretic, fungicide, hepatoprotective and vulnerary. Symphytum doesn't make the top plant list for this constituent. 

choline (root)-amount is not listed. The biological activities that most pertain to the use of comfrey are as follows: anti-cirrhotic, hepatoprotective, ileorelaxant, and lipotropic. Symphytum doesn't make the top plant list for this constituent. 

chromium (root) 8 ppm-this mineral plays a vital role in the metabolism of glucose in the body. It helps to synthesize cholesterol, fats and proteins. Symphytum does not make the top plant list for this constituent. 

cobalt (root) 129 ppm-this mineral plays an important role in assisting the body to assimilate and utilize vitamin B12. It participates in the production of red blood cells, boosts the cells ability to assimilate iron and it stimulates the production of enzymes required for a variety of body processes. Symphytum is number thirteen on the plant species with the highest amount of this constituent. 

consolicine (root)-the biological activities listed are CNS-paralytic, curaroid, myoparalytic and appears to have some toxicity to it. However, note that it doesn't even have a ppm or trace amount after the name-is there so little of this in the root as to barely make the chart? Symphytum is number one on the plant species with the highest amount of this constituent. 

consolidine (root) 17 ppm-the biological activities listed are CNS-Depressant, CNS-paralytic,curaroid and myoparalytic and they have some toxicity connected to them. Again, I notice the small amount found only in the root. Symphytum is number one on the plant species to contain this element in the highest amount. 

d-mannose (root)-amount not listed. This is a monosaccharide and plays a role in inducing interferon in the cells which helps in immunity. Symphytum is the number nine on the plant species list to have the highest amount of this constituent. 

echimidine (root)-amount not listed. This is another one of the toxic alkaloids because its biological activities are listed as hepatotoxic and mutagenic. Again, Symphytum is listed as the number one plant species to have the highest amount of this constituent. Note, too, that the amount available in the plant is not listed. 

echinatine (root)-amount not listed. There are no biological activities listed for this chemical and Symphytum (root) is the number two plant to contain this chemical in its highest amount. 

fat (root) 17,000 ppm-there are no biological activities reported. Symphytum does not make the top plant list for this constituent. 

fiber (root) 72,000 ppm-biological activities listed are anti-diabetic, anti-obesity, anti-tumor, anti-ulcer, cancer preventative, cardioprotective, hypocholesterolemic, hypotensive, and laxative. Symphytum does not make the top plant list for this constituent. 

GABA (root)-amount not listed. The biological activities are too numerous to repeat here but the ones that are relevant to the usage of Comfrey are sedative, tranquilizer, anti-stress, neurotransmitter, hypotensive, cardiovascular, diuretic, neuroinhibitor, CNS inhibitor, and anti-lethargic. Symphytum is number twenty-seven on the top plant species list. glucose (root)-amount not listed. The biological activities that are specific to Comfrey usage are anti-edemic, anti-hepatotoxic, anti-varicose. Symphytum doesn't make the top plant list for this constituent. 

glucuronic-acid (root)-amount not listed. The biological activities listed here are: antidote (camphor), antidote (morphine), anti-hepatotoxic and detoxicant. Symphytum is number eighteen on the top plant species list. 

gum (root) 50,000-100,000 ppm. There are no biological activities reported for gum. Symphytum is number six on the plant species list. 

heliosupine-n-oxide (root)-amount not listed. This appears to be one of the pyrrolizidine alkaloids because of the “n-oxide” attached to the name. Symphytum is number one on the plant species list. 

hypoxanthine (root)-there are no biological activities reported for this chemical. Symphytum is the number ten on the plant species list. 

iron (root) 810 ppm-this chemical is crucial to a healthy immune system because it carries oxygen from the lungs to all other bodily cells and tissues. Among many important bodily functions that are too numerous to mention, one function worthy of note is that it also boosts liver and kidney functions. Symphytum does not make the top plant list for this chemical. 

isobanerenol (root)-the amount is not listed and there are no biological activities reported. Symphytum is the number one plant highest in this constituent. 

kilocalories (root) 2,170/kg-there are no biological activities reported and Symphytum does not make the top plant species list. 

l-arabinose (root)-the amount is not listed and there are no biological activities reported, though this is a gum/simple sugar and therefore an energy provider. Symphytum is number twenty-three on the top plants list. 

l-rhamnose (root)-the amount is not listed and there are no biological activities listed. It is a gum/simple sugar and therefore provides energy. Symphytum is number twenty-three on the top plants list for this constituent. 

lasiocarpine (root)-there is not an amount listed. The biological activities present are anti-tumor, carcinogenic and hepatotoxic. Symphytum is number one on the top plants list for this constituent.

lithospermic-acid (root)-amount not listed. The biological activities are anti-gonadotrophic, anti-thyroid and cardiotonic. Symphytum is number five on the top plants list for this constituent. 

lycopsamine (root)-amount not listed. The biological activity is hepatotoxic and Symphytum is number two on the top plants list for this constituent. 

magnesium (root) 1,700 ppm-there is a myriad of benefits due to this chemical. The following are only a few of the ones that are more specific to the action of Comfrey: anti-convulsant, anti-inflammatory, anti-lithic, and anti-spasmodic. Symphytum is not listed on the top plants list for this chemical. 

manganese (root) 67 ppm-there is a myriad of benefits due to this chemical. The ones more closely related to the action of Comfrey are as follows: it is required for the breakdown of protein (of which Comfrey has a lot) and fats and is involved in bone growth and development; it is vital for the proper functioning of nerve health; it stimulates the production of antibodies and phagocytes which fight infection and disease. Symphytum is not listed on the top plants list for this chemical. 

mucilage (root) 290,000 ppm-the biological activities listed for this constituent are cancer-preventative and demulcent. Symphytum is number ten on the top plants list for this constituent. 

mucopolysaccharides (root) 250,000-300,000 ppm-there are no biological activities reported for this constituent, but this is a long sugar chain that stores energy. Symphytum is number one on the top plants list for this constituent. 

niacin (root)-no amount is listed. This is vitamin B3 and is necessary for a healthy nervous system and proper brain function. Among many important functions are the following: anti-convulsant, anti-dermatitic, anti-spasmodic, cancer-preventative, hepatoprotective, sedative. Symphytum is not listed on the top plants list for this constituent. 

octadecatetraenic-acid (seed)-no amount is listed and there are no biological activities reported for this constituent. Symphytum is number two on the top plants list for this constituent. 

phosphorus (root) 2,111 ppm-this is the second most plentiful mineral in the body next to calcium and most of it is located in the bones and teeth. It is essential to the proper development of bones, teeth and cells. It helps the body to utilize vitamins and helps to convert food to energy and it is an immuno-stimulant. Symphytum is not listed on the top plants list for this constituent. 

potassium (root) 15,900 ppm-the cell of the human body contains more potassium than any other mineral and it is essential for the chemical reactions that take place at the cellular level. It is important in the nervous system and works with sodium to maintain the proper acid/alkaline balance in the blood. It is an anti-fatigue and anti-spasmodic. Symphytum is not listed on the top plants list for this constituent. 

protein (root) 94,000 ppm-there are no biological activities reported for protein. Of course, proteins are the building blocks of life, so this is crucial to the action of Comfrey as a vulnerary. Symphytum is not listed on the top plants list for this constituent. 

pyrocatechins (root) 24,000 ppm-there are no biological activities reported for this constituent. Symphytum is number one on the top plants list for this constituent. 

reducing sugars (root) 51,500 ppm-there are no biological activities reported for this constituent. Symphytum is number four on the top plants list for reducing-sugars. 

riboflavin (root) 7.2 ppm-this is vitamin B2 which helps the body to digest fats, proteins and carbohydrates and convert them into usable energy. Among many of its benefits, it is necessary for cell respiration and growth, it facilitates the use of oxygen by body tissues and is thus vital to the repair of bodily tissues. It is also a cancer-preventative. Symphytum is not listed on the top plants list for this constituent. 

rosmarinic-acid (leaf) 5,000 ppm-the biological activities that are relevant to the usage of Comfrey are as follows: anti-bacterial, anti-hepatotoxic, anti-inflammatory, anti-oxidant, anti-shock, anti-viral and cancer-preventative. Symphytum is not listed on the top plants list for this constituent. 

selenium (root)-the amount is not listed. The biological activities that are relevant to the usage of Comfrey are as follows: analgesic, anti-cirrhotic, anti-oxidant, anti-ulcerogenic, cancer-preventative and fungicide. Symphytum is not listed on the top plants list for this constituent. 

silicic-acid (leaf) 40,000 ppm-the biological activity listed for this is anti-diabetic. Symphytum is number three on the top plants list for silicic-acid. 

silicon (root) 35 ppm-the biological activity listed is anti-arteriosclerotic. Symphytum is not listed on the top plants list for this constituent. 

sodium (root) 3,510 ppm-the biological activity listed is hypertensive. Symphytum is not listed on the top plants list for this constituent. 

stigmasterol (root)-the amount is not listed. The biological activities that pertain to the usage of Comfrey are as follows: anti-hepatotoxic, anti-inflammatory, anti-viral, cancer-preventative, and sedative. Symphytum is not listed on the top plants list for this constituent. 

sucrose (root)-the amount is not listed. The biological activities that pertain to the usage of Comfrey are as follows: anti-oxidant, demulcent, and vulnerary. Symphytum is not listed on the top plants list for this constituent. 

symlandine (plant)-the amount is not listed and no biological activities are reported. However, Symphytum is number one on the top plants list. 

symphytine (root)-the amount is not listed. The biological activity listed is hepatotoxic. Symphytum is number one on the top plants list. 

symphytocynoglossin (root) 21 ppm-the amount is not listed and no biological activities are reported. However, Symphytum is number one on the top plants list. 

tannin (plant) 80,000-90,000 ppm-the biological activities that pertain to the usage of Comfrey are as follows: anti-bacterial, anti-hepatotoxic, anti-oxidant, anti-viral, cancer-preventative, hepatoprotective and anti-HIV. Symphytum is not listed on the top plants list for this constituent. 

thiamin (root) 1.2 ppm-the biological activities that pertain to the usage of Comfrey are as follows: analgesic, anti-cardiospasmic, anti-deliriant, anti-fatigue and anti-neuralgic. Symphytum is not listed on the top plants list for this constituent. 

tin (root) 6.7 ppm-the biological activities listed are anti-acne and anti-bacterial. Symphytum is not listed on the top plants list for this constituent. 

viridiflorine (plant)-the amount is not listed and there are no biological activities reported. However, Symphytum is number one on the top plants list. 

water (root) 862,000 ppm-there are no biological activities listed for water, but it is important to remember that the body cannot function without water. It keeps all the systems functioning. Symphytum is not listed on the top plants list for this constituent. 

xylose (root)-the amount is not listed. The biological activities are anti-diabetic, diagnostic, and dye. Symphytum is not listed on the top plants list for this constituent. 

zinc (root) 2.8 pp-the biological activities that pertain to the usage of Comfrey are as follows: anti-arthritic, anti-eczemic, anti-infective, anti-viral, astringent, immuno-stimulant and vulnerary. Symphytum is not listed on the top plants list for this constituent



Z Phytother 2014; 35(06): 268-272
Beinwellsalbe
Klinischer Nutzen und Wirkmechanismus in der Haut
Federica Casetti1, Ute Wölfle1, Günter Seelinger2, Christoph M Schempp1

Eine Salbenzubereitung aus Beinwellkraut (Symphytum × uplandicum Nyman) wurde in einer offenen, nicht-interventionellen Studie an 24 Patienten mit leichten Gelenkschmerzen nach Trauma in einer Universitätsklinik getestet. Zweimal tägliches Auftragen über eine Woche führte zu deut­licher Besserung des Schmerzindex von 1,2 auf 0,5, gleichzeitig verbesserte sich die Hydratation der oberen Hautschichten signifikant. Einer der wirksamkeitsbestimmenden Inhaltsstoffe des Beinwells, Allantoin, hatte in experimentellen Untersuchungen an Zellkulturen mit Keratinozyten und primären Fibroblasten eine entzündungshemmende Wirkung. Sowohl Allantoin als auch die Vergleichssubstanz Diclofenac reduzierten die durch TNF-α oder simulierte solare Strahlung induzierte Freisetzung des proinflammatorischen Interleukins IL-6 mit effektiven Konzentrationen von ca. 50 µg/ml. Allantoin war nicht zytotoxisch und beeinträchtigte weder die Stoffwechselaktivität noch die Proliferationsrate der Hautzellen.

Comfrey ointment: clinical relevance and mode of action
A dermatological preparation from the aerial parts of comfrey (Symphytum x uplandicum Nyman) was investigated in an open, non-interventional study with 24 patients complaining about moderate arthralgia in a university hospital. Twice daily application for one week decreased the pain score from 1.2 to 0.5, while hydratization of the upper skin layers improved significantly. One of the main active components of Symphytum, allantoin, showed anti-inflammatory effects in experimental assays with dermal cell cultures, i.e. primary fibroblasts and keratinocytes. Allantoin as well as diclofenac reduced the release of pro-inflammatory interleukin IL-6 induced by TNF-α or solar simulated radiation, with effective concentrations of about 50 µm/ml. Allantoin was not cytotoxic, had no effects on cell metabolism and proliferation.



Wallwurz

Wallwurz (Symphytum officinale L., Boraginaceae) ist ein pflanzliches Arzneimittel, das äusserlich als Gel oder Salbe unter anderem bei rheumatischen Beschwerden, Muskel- und Gelenkschmerzen und nach Sportverletzungen aufgetragen wird. Zubereitungen mit Wallwurz wie Tees, Pulver oder Kapseln sollen nicht eingenommen werden, weil sie giftige Pyrrolizidinalkaloide enthalten können, die schwere unerwünschte Wirkungen verursachen. Bei äusserlicher Anwendung sind abgesehen von allergischen Reaktionen kaum Nebenwirkungen bekannt.
synonym: Beinwell, Symphytum officinale, Beinwellwurzel, Wallwurzsalbe, Wallwurzgel, Consolida maior

Stammpflanze
Die Gemeine Wallwurz oder Beinwell, Symphytum officinale L. (Boraginaceae), ist in Europa heimisch. Symphytum ist von sympho abgeleitet, „ich wachse zusammen“. Die Bezeichnungen Beinwell und Wallwurz sind auf das deutsche Verb „wallen“ zurückzuführen, was zusammenwachsen bedeutet. Bein bezeichnet ursprünglich Knochen. Die Namen widerspiegeln also die traditionelle Anwendung zur Heilung von Knochenbrüchen und Verletzungen. Wallwurz wurde auch als Düngemittel, Nahrungsmittel und Futterpflanze eingesetzt.

 Droge
Wallwurzsalben werden in der Regel aus der frisch geernteten Wurzel (Symphyti radix rec., Abbildung 4) und seltener aus dem Kraut (Symphyti herba) hergestellt. Als Synonym ist auch die Bezeichnung Consolidae radix statt Symphyti radix gebräuchlich, da die Pflanze auch als Consolida aior benannt wurde.

Inhaltsstoffe
Wallwurz enthält unter anderem Allantoin, Cholin, Gerbstoffe, Schleimstoffe, Saponine, Rosmarinsäurederivate und Pyrrolizidinalkaloide.

Wirkungen
Wallwurz werden reizlindernde, schmerzstillende, entzündungshemmende, granulationsfördernde, wundheilungsfördernde, antioedematöse und gerbende Effekte zugeschrieben. In den vergangenen Jahren wurden eine Reihe klinischer Studien durchgeführt, welche diese Wirkungen wissenschaftlich teilweise untermauern (vgl. Literatur). Gemäss mehrerer Studien sollen Wallwurzsalben ähnlich wirksam sein wie Diclofenac-Gele. 

Indikationen
Wallwurzsalben werden heute vor allem bei Schmerzen und Entzündungszuständen in Folge von Sportverletzungen (Prellungen, Zerrungen, Verstauchungen, Quetschungen, Hämatomen), bei rheumatischen Beschwerden, Arthritis, Arthrosen, Muskel- und Gelenkbeschwerden, Sehnenscheidenentzündungen, Rückenschmerzen, zur Nachbehandlung von Knochenbrüchen und Verrenkungen, Venenbeschwerden und Thrombophlebitis eingesetzt. Traditionell gibt es zahlreiche weitere Anwendungsgebiete, zum Beispiel die Wundheilungsförderung. Die Anwendung von Wallwurzsalben auf offenen Wunden ist gemäss Fachinformation aber kontraindiziert.

Dosierung
Die Arzneimittel werden 2-5 mal täglich äusserlich dünn aufgetragen und leicht einmassiert.

Kontraindikationen
Wallwurzsalben sollen nicht bei Überempfindlichkeit, auf offene Wunden, bei Kindern (keine Daten), während der Schwangerschaft und Stillzeit aufgetragen werden. Zubereitungen mit Wallwurz sollen aufgrund der toxischen Pyrrolizidinalkaloide nicht eingenommen werden, z.B. als Tee, Pulver oder in Form von Kapseln. Eine Ausnahme stellen stark verdünnte Homöopathika dar, in welchen diese Inhaltsstoffe nicht mehr nachweisbar sind. Gemäss der Kommission E Monographie soll Wallwurz nicht länger als 4-6 Wochen pro Jahr angewandt werden. In den Arzneimittel-Fachinformationen ist hingegen keine zeitliche Beschränkung angegeben, da in diesen Fertigarzneimitteln die Pyrrolizidinalkaloide entfernt wurden.

Unerwünschte Wirkungen
Die äusserliche Anwendung scheint im Allgemeinen gut verträglich zu sein. Nebenwirkungen sind, bis auf allergische Hautreaktionen, kaum bekannt. Bei innerlicher Anwendung sind aufgrund der Pyrrolizidinalkaloide schwere unerwünschte Wirkungen möglich, da diese Alkaloide lebertoxisch, mutagen und karzinogen sind. Entsprechende Fallbeispiele sind in der Literatur dokumentiert. Zubereitungen mit Wallwurz sollen deshalb nicht eingenommen werden (ausführliche Informationen finden sich bei Stickel, Seitz, 2000). Bei äusserlicher Anwendung auf intakter Haut scheint kein Risiko zu bestehen. Einige Hersteller verwenden zur Herstellung ihrer Wallwurzsalben Alkaloidarme Pflanzen und entfernen die Alkaloide beim Extraktionsprozess. Beim Sammeln wild wachsender Pflanzen besteht eine gewisse Verwechslungsgefahr mit dem giftigen roten Fingerhut, weil sich beide Pflanzen etwas ähneln.

Literatur
Arzneimittel-Fachinformation (CH, D)
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), 712-6Pubmed
Englert K., Mayer J.G., Staiger C. Symphytum officinale L. Zeitschrift für Phytotherapie, 2005, 26, 158–168
Giannetti B.M., Staiger C., Bulitta M., Predel H.G. 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), 637-41 Pubmed
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 Pubmed
Györik S., Stricker H. Severe pulmonary hypertension possibly due to pyrrolizidine alkaloids in polyphytotherapy. Swiss Med Wkly, 2009, 139(13-14), 210-1 Pubmed
Hänsel R., Sticher O., Steinegger E. Pharmakognosie - Phytopharmazie. Berlin, Heidelberg: Springer, 1999
Koll R., Buhr M., Dieter R., Pabst H., Predel H.G., 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, 11(6), 470-7 Pubmed
Kommission E Monographien
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), 681-92Pubmed
Lin C.C. et al. An outbreak of foxglove leaf poisoning. J Chin Med Assoc, 2010, 73(2), 97-100 Pubmed
Predel H.G., 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), 707-14 Pubmed
Staiger C. Comfrey: ancient and modern uses. Pharm J, 2007, 279, 732
Stickel F., Seitz H.K. The efficacy and safety of comfrey. Public Health Nutr, 2000, 3(4A), 501-8 Pubmed
Wichtl M. Teedrogen und Phytopharmaka. Stuttgart: Wissenschaftliche Verlagsgesellschaft, 1997



In Defence of Comfrey.      Margaret Whitelegg BA, MNIMH
The following paper was presented to the Department of Health and Ministry of Agriculture, Fisheries and Food by the National institute of Medical Herbalists in January, 1993. 

While evidence on pyrrolizidine alkaloid (PA) toxicity is mounting and the case against any PA-containing plant appears increasingly clear, the controversy over comfrey deserves closer inspection. It appears to be damned by its association with the effects of other PA containing plants, by the effects of its alkaloids on laboratory animals and by certain cases of hepatotoxicity through ingestion of the plant by humans. Yet I would argue that the case against comfrey is by no means proven in the scientific literature. 

Effects on Animals
Papers on the harmful effects of PAs on laboratory animals are legion, both those in other plant species 1-7 and in comfrey itself 8-11. One of the most often cited papers to this effect is that of Culvenor et al, "The structure and toxicity of the alkaloids of Russian Comfrey, a medicinal herb and item of human diet 12". He reported on an experiment in which alkaloids of comfrey were administered intraperitoneally to two-week old rats, either as a single dose or as multiple doses beginning at two weeks old over intervals of nine weeks. Evidence of hepatotoxicity was found. Bone13 and Pembery14 criticise this paper. Their criticisms reflect certain problems that occur repeatedly throughout the literature, whether proposing hepatotoxic, genotoxic or carcinogenic effects. Both authors suggest that two-week old rats are more vulnerable to the effects of PAs and, according to Jago,15 are particularly susceptible to the induction of megalocytosis. Pembery, for the Doubleday Institute, looks more closely at the numerical data and extrapolates equivalent quantities of PAs for humans, suggesting that exposure in humans at such levels is unlikely : 

"...it can be seen that the dose required to produce the least effect in the rats, reduced liver function, detectable by a change in the proportion of the plasma proteins, is equivalent to the alkaloid from 5,607 leaves if administered to a "man-sized rat" That is, if we assume that the effect of the alkaloid in man (sic) is going to be the same as in a young rat, apparently the most susceptible of any so far tested. If an average comfrey leaf is taken as 100g (and older leaves are much more than this), this dose level represents about eight times the body weight of the man-sized rat. Deaths occurred at levels equivalent to the alkaloid from 19,880 leaves or equivalent to 28 times the bodyweight of the man-sized rat. " 

More importantly, however - and this applies to all experiments with isolated alkaloids - both authors argue that to give alkaloids in isolation and injected intraperitoneally into animals, cannot reflect the effects in humans of the entire plant taken orally. This reflects one of the central tenets of herbal medicine, that an isolated chemical of a plant, while useful for certain indications, cannot define the action of the whole herb, where the herb is more than the sum of the individual parts, its constituents working synergistically to create its healing effects. A press release by the National Institute of Medical Herbalists 16, written by F. Fletcher Hyde, FNIMH, speaks of 

"...two insupportable assumptions. First, that the naturally occurring complex in the plant ... can be regarded as a mere physical dilution of alkaloids that the human metabolism is identical with that of the rat which is susceptible to these alkaloids, and not with the sheep which is resistant to them. " 

He makes a further point : 

"Tea, almonds, apples, pears, mustard, radishes and hops, to list only a few items, all contain substances which, if extracted, can be shown to be poisonous when tested under conditions similar to those used in the comfrey experiments. Must we then ignore our experience of the usefulness and wholesomeness of these foods because controlled trials and scientific evidence have not been published to establish their safety ? " 
While for orthodox medicine the laboratory experiments lead to a " universal knowledge", ie they are accessing the "pure" effects of a substance on the body, for herbalists, the context is all-important. The rigour of the laboratory finding may be more or less demonstrable, but the relevance of the findings to the effect of the whole herb is questionable. 
There are some striking examples, where research has been done, of synergistic effects in herbs. Ephedra sinica (Ma Huang) demonstrates this aspect clearly. According to Michael McIntyre17: 
"The Chinese herb Ma Huang is the source of the alkaloid ephedrine, which was for a time isolated from the herb and marketed by drug companies as a remedy for asthma. Once it came into widespread use, however, it soon became evident that the isolated drug had the disastrous side-effect of raising the blood pressure to dangerous levels, with the result that today it is hardly ever used to treat asthma. Yet in the whole plant there are some six other related alkaloids, one of which, pseudo-ephedrine, actually reduces the heart rate and lowers blood pressure. " 
Simon Mills,18 in Out of the Earth documents the same effect. A similar synergism is to be observed in Convallaria (lily of the valley) and Filipendula (meadowsweet). 
The main exception to the experiments with isolated alkaloids is that of Hirono et al19 where comfrey as a whole plant was fed to rats. Three groups of 19-28 inbred ACI rats were fed comfrey leaves for 480-600 days; four additional groups of 15-24 rats were fed comfrey root for varying lengths of time. Liver tumours were found in all groups except the controls, when autopsied at death. 
Yet even here when researchers used the whole plant, the results of the trial are extremely dubious. Bone13 and Pembery14 again question various aspects of the paper. PA levels were never measured, toxicity was admitted to vary. Diets of comfrey at certain levels are protein-deficient. 600 days is a long time in the life of a laboratory rat: according to Pembery 80% on a basal diet survive sixty days. The comparative control group survival was not indicated. Pembery again extrapolated figures and argues that the average rat consumed 24 times its own body weight at which level only one rat showed toxic symptoms. 
Bone's main criticism of the paper is the misleading nature of the title "Carcinogenic activity of Symphytum Officinale": in the text the comfrey is referred to as Russian comfrey, not officinale, so it is unclear which comfrey is on trial; but more importantly the tumours in all but three of the rats were benign; the plant appeared to be hepatotoxic, but not carcinogenic. Metastases were not mentioned, perhaps indicating that the three malignant tumours were of low malignancy. Malignancy occurred in the lower dosage groups, therefore a dose-response relationship was not evident. Abbott20 suggests that the relatively high doses that were used leave open the possibility of secondary effects that influenced the development of the cancers. Yet this paper is cited frequently in subsequent literature as concrete evidence of the carcinogenic properties of comfrey in animals. 

Other reports on comfrey fed directly to animals or applied topically report favourable effects, for example, Goldman et al21 report wound healing and analgesic properties of crude extracts of Symphytum officinale in rats. 

Taylor et al22 record protective effects of Symphytum officinale on mice bearing spontaneous and transplant tumours : 
"Mice bearing spontaneous tumours and receiving the plant extract survived an average of 59% longer than the controls. Of the mice surviving forty clays or more, 11% were controls and 44% were in the experimental group. The average increase in tumour size per day was 25% less in experimental mice as compared with controls. Spontaneous tumours in two mice receiving the plant extract regressed completely within two weeks of the treatment... Such regressions have not been observed in the large number of spontaneous tumours investigated in this laboratory for many years.... Transplant tumours were inhibited in 74% in association with the plant extract... The extract was not associated with any evidence of toxic effects. " 
Stamford et al23 report increase in prostaglandin-like material from isolated rat stomach from the effect of aqueous extracts of comfrey. 

Research on isolated comfrey, after the nature of the PA experiments, also indicate positive chemicals of effects. Rosmarinic acid was isolated from Symphytum officinale and its antiinflammatory properties reported by Gracza et al24. Much work has been done on the effects of allantoin. Bone13 cites a number of papers on this topic: for example, McAlister25 found it stimulated epithelial regrowth, effectively removed necrotic tissue and caused local and internal leucocytosis; Kaplan26 and Greenbaum27 report accelerated healing of wounds and ulcers by the stimulation of granulation tissue formation; Loots recorded that allantoin significantly increased cellular multiplication in damaged nerves in rats after oral administration. Moreover similar experiments on other herb extracts have shown a hepato-protective effect, most notably Carduus marianus (milk thistle), documented eg in Vogel G et al28, Hruby K et al29 and Tuchweber B et al30. 

Effects In Humans 
Cases of PA poisoning in humans are again legion 31-34. Despite the obvious toxicity of the PAs, before the mid 1980s the defenders of comfrey were able to claim that no cases of poisoning by comfrey had ever been discovered. All the cases cited had been instances of poisoning by other genera. But since then four cases have come to light which implicate comfrey directly. 

Case 1 : (Ridker, McDermott et al 35.) A forty-nine year old woman was admitted to hospital with progressive swelling of the abdomen and extremeties over the preceeding four months. Veno-occlusive disease was eventually diagnosed, allegedly caused by chronic exposure to PAs consumed in a comfrey powder, estimated at a minimum of 85mg of PAs over the previous six month period. There were other possible causes for her illness : she was a heavy consumer of herbs, vitamins and "natural" food supplements. 
These included daily supplementations of vitamins C, K, E, A, and B complex, calcium, magnesium, potassium, zinc, iron, lecithin and stereotrophic adrenal bovine extract. She drank three cups of chamomile tea per week and for the six months before admission had consumed one quart a day of a herbal tea known as Mu-16. In addition, for the four months before admission, she had taken two capsules of "comfey-pepsin pills" with each meal. In analysing the case, only the Mu-tea and comfrey were considered as the harmful agents. The authors admit "...it is possible that she had other sources of exposure...," yet conclude "To our knowledge, this is the first report of veno-occlusive disease in any human after the use of a preparation claiming to be made from comfrey." 

Case 2 : (Weston, Cooper et al36 )A thirteen-year old boy was admitted into hospital with symptoms which were found to be caused by veno-occlusive disease. He had been suffering from Crohn's disease for three years and had been treated with prednisolone and sulphasalazine which removed symptoms. At his parents' request the drugs were discontinued and he was treated with acupuncture and comfrey root prescribed by a naturopath. Exact quantities and frequency are unknown. He had a further course of prednisolone in 1984. When admitted to hospital he was taking prednisolone and sulphasalazine. The authors point out that major hepatic vein thrombosis, but not veno-occlusive disease has been described in patients with colitis; they concede that the patient may have been more susceptible to hepatic veno-occlusive disease because of underlying bowel disease causing malnutrition, but they conclude that "the only possible causal factor in this patient was comfrey". The drugs are not considered as possible factors. 

Case 3 : (Bach, Swan et al37.) A forty-seven year old white non-alcoholic woman began to feel unwell in 1978 with vague abdominal pain, fatigue and allergies. A homeopathic doctor recommended comfrey tea. She consumed as many as ten cups per day in addition to taking comfrey pills by the handful, which continued for more than one year. Four years later, in 1982, serum aminotransferase levels were twice normal range. By 1986 she had further signs of liver disease. In this case it is not clear what the woman first presented with, nor how long before the development of the liver abnormalities she stopped taking comfrey. In a case of addiction such as this, deleterious effects are nevertheless counted as condemning the plant taken in normal, moderate doses. 

Case 4 : (Yeong, Swinburn et al38.) A twenty-three year old man presented with veno-occlusive disease and severe portal hypertension and subsequently died from liver failure. He had eaten comfrey leaves for some time before his illness. The man presented with a three-month history of initial influenza-like symptoms followed by continued malaise and night sweats. Three weeks before admission he noticed peripheral oedema and abdominal distension. For four years prior to illness he had been living in a commune and had eaten a predominantly vegetarian diet. He had a striking "binge-type" eating pattern whereby he would eat large quantities of a particular food such as grapes or cashews for days and weeks on end. In the one to two weeks before the onset of symptoms he ate four to five steamed young comfrey leaves as a vegetable every day. The conclusion again is poisoning by comfrey. The details of the case are again not clear. It is not stated whether he ingested comfrey one to two weeks before the onset of the initial flu-like symptoms, or of the more recent oedema and distension. The authors suggest that the patient's protein deficient diet could have played a contributory role and admit that "marked individual variations in dosage susceptibility have been found with other PAs." Abbott20 declines to consider this case in his report because "there is some controversy surrounding this case." 

None of the above cases are uncomplicated; each involves either abuse or other possible sources of toxicity. The link to comfrey cannot be made without considerable qualification. 

One can find similar cases of abuse or harmful effects of orthodox medicines throughout the medical literature, but this does not necessarily lead to withdrawal or limitation of the drug. 

In an exchange of letters in the American Journal of Medicine39, two cases of acute pancreatitis induced by erythromycin are discussed. While the differences between the cases are outlined, their common feature appears to account adequately for the anomaly of the reaction; "Both cases occurred as a result of above-normal doses ... Therefore ... acute pancreatitis is probably an adverse effect encountered only with above-normal doses." 
Herbalists are castigated for their reliance on tradition as proof of safety of their remedies. In a paper by Larrey et al40, discussing cases of hepatitis after Germander administration, case three described a man who had taken Germander to lose weight and who was also taking dexfenfluramine. The authors do not rule out the latter as a cause of the man's hepatitis, but suggest that "this drug has been marketed for several years and has not been reported to be hepatotoxic". 
The use of metronidazole was continued indefinitely in a patient with inflammation of an ileostomy despite the possibility that long-term use might be carcinogenic as indicated by tests on rats41. 
The Independent of 9th Sept, 199242 reported that about 30,000 people are admitted to hospital each year with bleeding ulcers. About 3000 of them die. Between 20-30% of the fatalities are caused by non-steroidal anti-inflammatory drugs (NSAIDS). GPs are aware of the risks of NSAIDS but there has been no reduction in the twenty-four million prescriptions written each year. 

Abbott20 suggests that the outbreaks of poisoning and the case report studies provide some indication of the dangerous dosage levels for short-term exposure, but he expresses concern about difficulties in assessing the long-term, low-dose exposure risks. This concern is echoed in other reports. Yet the data to establish possible occurrence of veno-occlusive disease with low doses of PAs over a long time are based either on isolated PA experiments with animals, or on effects on humans of other plants containing PAs and cannot therefore be conclusive in relation to the effects of comfrey. 

There are no reported cases of cancer in humans as a result of ingestion of comfrey. 
Although it is difficult to establish any causal link in cases of cancer, it is interesting to note in this respect that in Jamaica, even though the incidence of liver lesions, particularly veno-occlusive disease, is high, cases of liver cancer are rare.  Anderson and McLean43 report on an interesting study, albeit small and non-random, which considers liver function in humans after comfrey ingestion. Blood tests were done on humans who had been taking comfrey for varying amounts of time and in various quantities and preparations. Their findings were: 
"Results of liver function tests in the 29 volunteers were found to be within normal range by the local laboratories wish the exception of a slight elevation in bilirubin levels in two and AST in one sample. Alpha-foeto-protein levels were normal in the seven volunteers tested. There is no evidence of liver injury in this small sample, even for those who have been regularly taking the herb for 20 years." 
In addition to the more specific points raised in the various papers on comfrey toxicity, there are a number of general comments that can be made on aspects of the comfrey "file". 

Despite claims that the rigour of science is being applied to the investigation of the plant, there is much uncertainty within the debate, and the uncertainty is often ignored. The levels of PAs in the leaves and roots are never the same in any two experiments, indeed never the same in any two leaves. The young leaves have a higher level, the mature ones lower; levels in the leaves vary seasonally, being higher in spring. The effects of alkaloids on a variety of animals differ: according to Pembery14 the LD50 of retrosine in male rats is about 40mg/kg body weight, whereas guineapigs had no liver damage at 420mg/kg. 

There is imprecision: Yeong11 describes his later work on rats as "Three groups of young adult rats were fed PAs derived from Russian comfrey to study the effects of the herb (my italics) on the liver" - the effects of the herb are not those of just the PAs. McDermott and Ridker present a very partial case history of their patient in their 1990 paper44, omitting much information that might alter interpretation of the case. 
The various methods of extraction of the alkaloids and their administration to the rats are not questioned in terms of effect on the comfrey product. Yeong11, for example says: 
"The plant material was extracted exhaustively with methanol and the filtered extract was reduced in volume. The precipitated allantoin was filtered off and the methanol removed in vacuo. The residue was dissolved in acid, washed with hexane and ether, treated with zinc dust to reduce the N-oxides, made alkaline and extracted with chloroform... the rats in group 1 were each fed by lavage, a single dose of 200mg/kg alkaloid dissolved in 3ml of 0.1 M hydrochloric acid..." 
The citing of earlier papers proceeds on the assumption of certainty, which, as we have seen, is not always as sure as it is portrayed. According to Bone and Pembery, Mohabbat31, Culvenor12 and Hirono19 are flawed to some extent, yet their conclusions are interpreted as sure. In particular, as mentioned above, Hironots paper is regularly quoted as proof of the carcinogenicity of comfrey. In 1978, L. Hills of the Doubleday Institute published an article, reported in the BMJ 197945, which concluded that until further research clarified the long-term health hazards of comfrey ingestion, "no human being or animal should eat, drink, or take comfrey in any form." The report by Pembety14 was subsequently published in 1982 in which the foreword by Hills revoked the 1978 report and comfrey was declared safe. Many post 1982 papers on comfrey quote the 1978 warning and fail to acknowledge the 1982 revocation. 

Conclusion.
This review of some of the literature on the comfrey controversy is by no means exhaustive. 
Rather than examining the finer details of all the papers, which would be a huge task, it set out to make a few points about the general nature of the debate from the herbalistt s point of view and to suggest from that how the validity of the evidence against comfrey might be doubted. 
When considered among the mass of PA literature the evidence may look convincing, but if the data concerning comfrey itself is isolated, the arguments for its toxicity are far from conclusive. As herbalists, we would question the data obtained from application of the isolated alkaloid as not reflecting the action of the whole herb. When separated from information on poisoning due to other plants, there remain only four cases implicating comfrey in toxicity. None of these are uncomplicated and none can be pressed without qualification. The long-term, low dose effects remain unproven. 
Towards the end of 1992, a number of herbalists from the Council of the National Institute of Medical Herbalists discussed the comfrey issue on the basis of the main literature on the debate. While not denying the toxicity of PAs in isolation, we consider that the evidence in the case of comfrey does not warrant its withdrawal from use by professional medical herbalists prescribing to individual patients under the terms of the 1968 Medicines Act. We consider that, with restrictions recommended by the Institute to our members in terms of amount per week and length of time prescribed, the continued use of the herb is safe in our hands. 
As an extra precaution, and for our own interest and benefit, we shall be instigating research into hepatototoxicity in the near future and monitoring patients with potential liver lesions by means of blood-sample analysis. On the basis of the evidence in the comfrey file it would be an inexpressible loss to withdraw a herb as versatile as comfrey from use by herbalists. 

Margaret Whitelegg is Director of Research of the National Institute of Medical Herbalists. She practises in Lancaster. 

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