Skip to main content Accessibility help
×
Home
Hostname: page-component-7f7b94f6bd-9g8ph Total loading time: 0.46 Render date: 2022-07-01T05:43:26.691Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "useRatesEcommerce": false, "useNewApi": true } hasContentIssue true

The efficacy and safety of comfrey

Published online by Cambridge University Press:  02 January 2007

Felix Stickel*
Affiliation:
Department of Medicine I, Division of Gastroenterology and Hepatology, University of Erlangen-Nuernberg, Krankenhausstrasse 12, 91054 Erlangen, Germany
Helmut K Seitz
Affiliation:
Laboratory of Alcohol Research, Salem Medical Center, University of Heidelberg, Germany
*
*Corresponding author: Email felix.stickelamed1.med.uni-erlangen.de
Rights & Permissions[Opens in a new window]

Abstract

HTML view is not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Herbal medication has gathered increasing recognition in recent years with regard to both treatment options and health hazards. Pyrrolizidine alkaloids have been associated with substantial toxicity after their ingestion as tea and in the setting of contaminated cereals have led to endemic outbreaks in Jamaica, India and Afghanistan. In Western Europe, comfrey has been applied for inflammatory disorders such as arthritis, thrombophlebitis and gout and as a treatment for diarrhoea. Only recently was the use of comfrey leaves recognized as a substantial health hazard with hepatic toxicity in humans and carcinogenic potential in rodents. These effects are most likely due to various hepatotoxic pyrrolizidine alkaloids such as lasiocarpine and symphytine, and their related N-oxides. The mechanisms by which toxicity and mutagenicity are conveyed are still not fully understood, but seem to be mediated through a toxic mechanism related to the biotransformation of alkaloids by hepatic microsomal enzymes. This produces highly reactive pyrroles which act as powerful alkylating agents. The main liver injury caused by comfrey (Symphytum officinale) is veno-occlusive disease, a non-thrombotic obliteration of small hepatic veins leading to cirrhosis and eventually liver failure. Patients may present with either acute or chronic clinical signs with portal hypertension, hepatomegaly and abdominal pain as the main features.

Therapeutic approaches include avoiding intake and, if hepatic failure is imminent, liver transplantation. In view of the known serious hazards and the ban on distributing comfrey in Germany and Canada, it is difficult to understand why comfrey is still freely available in the United States.

Type
Research Article
Copyright
Copyright © CABI Publishing 2000

References

1: Brown, JS, Marcy, SA. The use of botanicals for health purposes by members of a prepaid health plan. Res. Nurs. Health 1991; 14: 339–50.CrossRefGoogle ScholarPubMed
2: Moore, J, Phipps, K, Marcer, D, Lewith, G.Why do people seek treatment by alternative medicine?. Br. Med. J. 1985; 290: 28–9.CrossRefGoogle ScholarPubMed
3: Winslow, LC, Kroll, DJ. Herbs as medicine. Arch. Intern. Med. 1998; 158: 2192–9.CrossRefGoogle Scholar
4: Schuppan, D, Jia, JD, Brinkhaus, B, Hahn, EG. Herbal products for liver disease: a therapeutic challenge for the new millennium. Hepatology 1999; 30: 1099–104.CrossRefGoogle ScholarPubMed
5: Trevelyan, J.Herbal medicine. Nurs. Times 1993; 89: 36–8.Google ScholarPubMed
6: Schiano, T. Liver injury from herbs and other botanicals. In: Gitlin, N, ed. Clinics in Liver Disease, vol. 2. Chicago: W.B. Saunders, 1998: 607–30.Google Scholar
7: Smith, LW, Culvenor, CCJ. Plant sources of hepatotoxic pyrrolizidine alkaloids. J. Nat. Prod. 1981; 44: 129–52.CrossRefGoogle ScholarPubMed
8: Wilmot, FC, Robertson, GW. Senecio disease or cirrhosis of the liver due to senecio poisoning. Lancet 1920; II, 828828.Google Scholar
9: Selzer, G, Parker, RGF. Senecio poisoning exhibiting as Chiari's syndrome. Am. J. Pathol. 1951; 27: 885907.Google ScholarPubMed
10: Bras, G, Jeliffe, DB, Stuart, KL. Veno-occlusive disease of the liver with non-portal type of cirrhosis, occurring in Jamaica. AMA Arch. Pathol. 1954; 57: 285300.Google Scholar
11: Mohabat, O, Srivastava, RN, Younos, MS, Gholam Gsediq, GG, Merzad, AA, Aram, GN. An outbreak of hepatic veno-occlusive disease in north-western Afghanistan. Lancet 1976; 2: 269–71.CrossRefGoogle Scholar
12: Tandon, BN, Tandon, RK, Tandon, HD, Narndranathan, M.An epidemic of veno-occlusive disease of liver in central India. Lancet 1976; 2: 271–2.CrossRefGoogle ScholarPubMed
13: Stillman, AS, Huxtable, RJ, Consroe, P, Kohnen, P, Smith, S.Hepatic veno-occlusive disease due to pyrrolizidine (Senecio) poisoning in Arizona. Gastroenterology 1977; 73: 349–52.Google ScholarPubMed
14: Fox, DW, Hart, MC, Bergeson, PS, Jarrett, PB, Stillman, AE, Huxtable, RJ. Pyrrolizidine (Senecio) intoxication mimicking Reye's syndrome. J. Paediatr. 1978; 93: 980–2.CrossRefGoogle Scholar
15: Ridker, PM, Ohkuma, S, McDermott, WV, Trey, C, Huxtable, RJ. Hepatic venoocclusive disease associated with the consumption of pyrrolizidine-containing dietary supplements. Gastroenterology 1985; 88: 1050–4.CrossRefGoogle Scholar
16: Weston, CFM, Cooper, BT, Davies, JD. Veno-occlusive disease of the liver secondary to ingestion of comfrey. Br. Med. J. 1987; 295: 183.CrossRefGoogle ScholarPubMed
17: Bach, N, Thung, SN, Schaffner, F.Comfrey herb tea-induced hepatic veno-occlusive disease. Am. J. Med. 1989; 87: 97–9.CrossRefGoogle ScholarPubMed
18: Prakash, AS, Pereira, TN, Reilly, PE, Seawright, AA. Pyrrolizidine alkaloids in human diet. Mutat. Res. 1999; 15 (443): 5367.CrossRefGoogle Scholar
19: Comfrey In: The Lawrence Review of Natural Products Monograph System. Pharmaceutical Information Associates, 1987;.Google Scholar
20: Roitman, JN. Comfrey and liver damage. Lancet 1981; 1: 944.CrossRefGoogle ScholarPubMed
21: Huxtable, RJ, Lüthy, J, Zweifel, U.Toxicity of comfrey-pepsin preparations. N. Engl. J. Med. 1986; 315: 1095.Google ScholarPubMed
22: Ahmad, VU, Noorwala, M, Mohammad, FV, Sener, B.A new triterpene glycoside from the roots of Symphytum officinale. J. Nat. Prod. 1993; 56: 329–34.CrossRefGoogle ScholarPubMed
23: Ahmad, VU, Noorwala, M, Mohammad, FV, Sener, B, Gilani, AH, Aftab, K.Symphytoxide A, a triterpenoid saponin from the roots of Symphytum officinale. Phytochemistry 1993; 32: 1003–6.CrossRefGoogle ScholarPubMed
24: Stegelmeier, BL, Edgar, JA, Colegate, SM, Gardner, DR, Schoch, TK, Coulombe, RA et al. Pyrrolizidine alkaloid plants, metabolism and toxicity. J. Nat. Toxins 1999; 8: 95116.Google ScholarPubMed
25: Betz, JM, Eppley, RM, Taylor, WC, Andrzejewski, D.Determination of pyrrolizidine alkaloids in commercial comfrey products (Symphytum sp.). J. Pharm. Sci. 1994; 83: 649–53.CrossRefGoogle Scholar
26: Mattocks, AR. Toxic pyrrolizidine alkaloids in comfrey. Lancet 1980; 2: 1136.CrossRefGoogle ScholarPubMed
27: Nebert, DW, Nelson, DR, Coon, MJ, Estabrook, RW, Feyereisen, R, Fuji-Kuriyama, Y et al. The P450 superfamily: update on new sequences, gene mapping, and recommended nomenclature. DNA Cell Biol. 1991; 10: 114.CrossRefGoogle ScholarPubMed
28: Huxtable, RJ. New aspects of the toxicology and pharmacology of pyrrolizidine alkaloids. Gen. Pharmacol. 1979; 10: 159–67.CrossRefGoogle ScholarPubMed
29: Couet, CE, Hopley, J, Hanley, AB. Metabolic activation of pyrrolizidine alkaloids by human, rat and avocado microsomes. Toxicon 1996; 34: 1058–61.CrossRefGoogle ScholarPubMed
30: Mattocks, AR. Chemistry and Toxicology of Pyrrolizidine Alkaloids, London: Academic Press, 1986: 1.Google Scholar
31: McLean, EK. Senecio and other plants as liver poisons. Isr. J. Med. Sci. 1974; 10: 436–40.Google Scholar
32: Mattocks, AR. Spectrophotometric determination of pyrrolizidine alkaloids – some improvements. Anal. Chem. 1968; 40: 1749–50.CrossRefGoogle ScholarPubMed
33: Brauchli, J, Lüthy, J, Zweifel, U, Schlatter, C.Pyrrolizidine alkaloids from Symphytum officinale L. and their percutaneous absorbtion in rats. Experientia 1982; 38: 1085–7.CrossRefGoogle Scholar
34: Couet, CE, Crews, C, Hanley, AB. Analysis, separation, and bioassay of pyrrolizidine alkaloids from comfrey (Symphytum officinale). Nat. Toxins 1996; 4: 163–7.CrossRefGoogle Scholar
35: Lin, G, Zhou, KY, Zhao, XG, Wang, ZT, But, PP. Determination of hepatotoxic pyrrolizidine alkaloids by on-line high performance liquid chromatography mass spectrometry with an electrospray interphase. Rapid Commun. Mass Spectrom. 1998; 12: 1445–56.3.0.CO;2-G>CrossRefGoogle Scholar
36: Roulet, M, Laurini, R, Rivier, L, Calame, A.Hepatic veno-occlusive disease in a newborn infant of a woman drinking herbal tea. J. Pediatr. 1988; 2: 481500.Google Scholar
37: Sperl, W, Stuppner, H, Gassner, J, Judmaier, W, Dietze, O, Vogel, W.Reversible hepatic veno-occlusive disease in an infant after consumption of pyrrolizidine-containing herbal tea. Eur. J. Pediatr. 1995; 154: 112–16.CrossRefGoogle Scholar
38: Essell, JH, Thomson, JM, Harman, GS, Halvorson, RD, Snyder, MJ, Johnson, RA et al. Marked increase in veno-occlusive disease of the liver associated with methotrexate use for Graft-Versus-Host disease prophylaxis in patients receiving busulfan/cyclophosphamide. Blood 1992; 79: 2784–8.Google ScholarPubMed
39: Fried, MW, Connaghan, DG, Sharma, S, Martin, LG, Devine, S, Holland, K et al. Tranjugular intrahepatic portosystemic shunt for the management of severe venoocclusive disease following bone marrow transplantation. Hepatology 1996; 24: 588–91.CrossRefGoogle Scholar
40: Alpert, LI. Veno-occlusive disease of the liver associated with oral contraceptives: case report and review of the literature. Hum. Pathol. 1976; 7: 709–-18.CrossRefGoogle Scholar
41: Pappas, SC, Malone, DG, Rabin, L, Hoofnagel, YH, Jones, EA. Hepatic veno-occlusive disease in a patient with systemic lupus erythematosus. Arthritis Rheum. 1984; 27: 104–8.CrossRefGoogle Scholar
42: Goodman, ZD, Ishak, KG. Occlusive venous lesions in alcoholic liver disease. Gastroenterology 1982; 83: 786–96.Google ScholarPubMed
43: Rollins, BJ. Hepatic veno-occlusive disease. Am. J. Med. 1990; 81: 297306.CrossRefGoogle Scholar
44: Shulman, HM, Fisher, LB, Schoch, HG, Henne, KW, McDonald, GB. Venooclusive disease of the liver after marrow transplantation: histological correlates of clinical sign and symptoms. Hepatology 1994; 19: 1171–80.CrossRefGoogle Scholar
45: Sherlock, S.Noncirrhotic extrahepatic and intrahepatic portal hypertension. Semin. Liver Dis. 1982; 2: 202–10.CrossRefGoogle ScholarPubMed
46: Yeong, ML, Wakefield, St J, Ford, HC. Hepatocyte membrane injury and bleb formation following low dose comfrey toxicity in rats. Int. J. Exp. Pathol. 1993; 74: 211–17.Google ScholarPubMed
47: Brooks, SEH, Miller, CG, McKenzie, K, Audretsch, JJ, Bras, G.Acute veno-occlusive disease of the liver. Arch. Pathol. 1970; 89: 507–20.Google ScholarPubMed
48: Franke, H.Substructural alterations of liver parenchymal cells induced by xenobiotics. Exp. Pathol. 1990; 39: 139–55.CrossRefGoogle ScholarPubMed
49: Jewell, S, Bellomo, G, Thor, H, Orrenius, S.Bleb formation in hepatocytes during drug metabolism is caused by disturbances in thiol and calcium ion homeostasis. Science 1982; 217: 1257–8.CrossRefGoogle ScholarPubMed
50: Miskelly, FG, Goodyer, LI. Hepatic and pulmonary complications of herbal medicines. Postgrad. Med. J. 1992; 68: 935–6.CrossRefGoogle ScholarPubMed
51: Shubat, PJ, Banner, W, Huxtable, RJ. Pulmonary vascular response induced by the pyrrolizidine alkaloid monocrotaline in rats. Toxicon 1987; 25: 9951002.CrossRefGoogle ScholarPubMed
52: Guzowski, DE, Solgado, ED. Changes in main pulmonary artery of rats with monocrotaline induced pulmonary hypertension. Arch. Pathol. Lab. Med. 1987; 111: 741–5.Google ScholarPubMed
53: Hirono, I, Haga, M, Fujii, M, Mori, H.Induction of hepatic tumors in rats by senkirkine and symphytine. J. Natl. Cancer Inst. 1979; 63: 469–72.Google ScholarPubMed
54: Petry, TW, Bowden, GT, Huxtable, RJ, Sipes, IG. Characterization of hepatic DNA damage induced in rats by the pyrrolizidine alkaloid monocrotaline. Cancer Res. 1984; 44: 1505–9.Google ScholarPubMed
55: Behninger, C, Abel, G, Roder, E, Neuberger, V, Goggelmann, W.Studies on the effect of an alkaloid extract of Symphytum officinale on human lymphocyte cultures. Planta Med. 1989; 55: 518–22.CrossRefGoogle ScholarPubMed
56: Olinescu, A, Manda, G, Neagu, M, Hristescu, M, Dasanu, C.Action of some proteic and carbohydrate components of Symphytum officinale upon normal and neoplastic cells. Roum. Arch. Microbiol. Immunol. 1993; 52: 7380.Google ScholarPubMed
57: Culvenor, CC. Estimated intakes of pyrrolizidine alkaloids by humans. A comparison with dose rates causing tumors in rats. J. Toxicol. Environ. Health 1983; 11: 625–35.CrossRefGoogle ScholarPubMed
58: Zimmermann, HJ, Lewis, JH. Chemical and toxin-induced liver disease. Gastroenterol. Clin. N. Am. 1995; 24: 739.Google Scholar
59: Larrey, D.Hepatotoxicity of herbal remedies. J. Hepatol. 1997; 26: 4754.CrossRefGoogle ScholarPubMed
60: Eltumi, M, Trivedi, P, Hobbs, JR, Portman, B, Cheeseman, P, Downie, C et al. Monitoring of venoocclusive disease after bone marrow transplantation by serum aminopropeptide of type III procollagen. Lancet 1993; 342: 518–21.CrossRefGoogle Scholar
61: Lassau, N, Leclére, J, Auperin, A, Bourhis, JH, Hartman, O, Valteau-Couanet, D et al. Hepatic veno-occlusive disease after myoablative treatment and bone marrow transplantation: value of Gray-scale and Doppler US in 100 patients. Radiology 1997; 204: 545–52.CrossRefGoogle Scholar
62: Mowat, AP. Biliary disorders in childhood. Semin. Liver Dis. 1982; 2: 271–81.CrossRefGoogle ScholarPubMed
63: Fried, MW, Connaghan, DG, Sharma, S, Martin, LG, Devine, S, Holland, K et al. Transjugular intrahepatic portosystemic shunt for the management of severe venoocclusive disease following bone marrow transplantation. Hepatology 1996; 24: 588–91.CrossRefGoogle ScholarPubMed
64: Norris, S, Crosbie, O, McEntee, G, Traynor, O, Molan, N, McCann, S et al. Orthotopic liver transplantation for veno-occlusive disease complicating autologous bone marrow transplantation. Ransplantation 1997; 63: 1521–4.CrossRefGoogle ScholarPubMed
65: Huxtable, RJ. The myth of beneficient nature: the risks of herbal preparations. Ann. Int. Med. 1992; 117: 165–6.CrossRefGoogle Scholar
You have Access
95
Cited by

Save article to Kindle

To save this article to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

The efficacy and safety of comfrey
Available formats
×

Save article to Dropbox

To save this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about saving content to Dropbox.

The efficacy and safety of comfrey
Available formats
×

Save article to Google Drive

To save this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about saving content to Google Drive.

The efficacy and safety of comfrey
Available formats
×
×

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *