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The efficacy and safety of comfrey

  • Felix Stickel (a1) and Helmut K Seitz (a2)


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.

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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.
2: Moore, J, Phipps, K, Marcer, D, Lewith, G.Why do people seek treatment by alternative medicine?. Br. Med. J. 1985; 290: 28–9.
3: Winslow, LC, Kroll, DJ. Herbs as medicine. Arch. Intern. Med. 1998; 158: 2192–9.
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.
5: Trevelyan, J.Herbal medicine. Nurs. Times 1993; 89: 36–8.
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.
7: Smith, LW, Culvenor, CCJ. Plant sources of hepatotoxic pyrrolizidine alkaloids. J. Nat. Prod. 1981; 44: 129–52.
8: Wilmot, FC, Robertson, GW. Senecio disease or cirrhosis of the liver due to senecio poisoning. Lancet 1920; II, 828828.
9: Selzer, G, Parker, RGF. Senecio poisoning exhibiting as Chiari's syndrome. Am. J. Pathol. 1951; 27: 885907.
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.
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.
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.
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.
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.
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.
16: Weston, CFM, Cooper, BT, Davies, JD. Veno-occlusive disease of the liver secondary to ingestion of comfrey. Br. Med. J. 1987; 295: 183.
17: Bach, N, Thung, SN, Schaffner, F.Comfrey herb tea-induced hepatic veno-occlusive disease. Am. J. Med. 1989; 87: 97–9.
18: Prakash, AS, Pereira, TN, Reilly, PE, Seawright, AA. Pyrrolizidine alkaloids in human diet. Mutat. Res. 1999; 15 (443): 5367.
19: Comfrey In: The Lawrence Review of Natural Products Monograph System. Pharmaceutical Information Associates, 1987;.
20: Roitman, JN. Comfrey and liver damage. Lancet 1981; 1: 944.
21: Huxtable, RJ, Lüthy, J, Zweifel, U.Toxicity of comfrey-pepsin preparations. N. Engl. J. Med. 1986; 315: 1095.
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.
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.
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.
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.
26: Mattocks, AR. Toxic pyrrolizidine alkaloids in comfrey. Lancet 1980; 2: 1136.
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.
28: Huxtable, RJ. New aspects of the toxicology and pharmacology of pyrrolizidine alkaloids. Gen. Pharmacol. 1979; 10: 159–67.
29: Couet, CE, Hopley, J, Hanley, AB. Metabolic activation of pyrrolizidine alkaloids by human, rat and avocado microsomes. Toxicon 1996; 34: 1058–61.
30: Mattocks, AR. Chemistry and Toxicology of Pyrrolizidine Alkaloids, London: Academic Press, 1986: 1.
31: McLean, EK. Senecio and other plants as liver poisons. Isr. J. Med. Sci. 1974; 10: 436–40.
32: Mattocks, AR. Spectrophotometric determination of pyrrolizidine alkaloids – some improvements. Anal. Chem. 1968; 40: 1749–50.
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.
34: Couet, CE, Crews, C, Hanley, AB. Analysis, separation, and bioassay of pyrrolizidine alkaloids from comfrey (Symphytum officinale). Nat. Toxins 1996; 4: 163–7.
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.
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.
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.
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.
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.
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.
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.
42: Goodman, ZD, Ishak, KG. Occlusive venous lesions in alcoholic liver disease. Gastroenterology 1982; 83: 786–96.
43: Rollins, BJ. Hepatic veno-occlusive disease. Am. J. Med. 1990; 81: 297306.
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.
45: Sherlock, S.Noncirrhotic extrahepatic and intrahepatic portal hypertension. Semin. Liver Dis. 1982; 2: 202–10.
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.
47: Brooks, SEH, Miller, CG, McKenzie, K, Audretsch, JJ, Bras, G.Acute veno-occlusive disease of the liver. Arch. Pathol. 1970; 89: 507–20.
48: Franke, H.Substructural alterations of liver parenchymal cells induced by xenobiotics. Exp. Pathol. 1990; 39: 139–55.
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.
50: Miskelly, FG, Goodyer, LI. Hepatic and pulmonary complications of herbal medicines. Postgrad. Med. J. 1992; 68: 935–6.
51: Shubat, PJ, Banner, W, Huxtable, RJ. Pulmonary vascular response induced by the pyrrolizidine alkaloid monocrotaline in rats. Toxicon 1987; 25: 9951002.
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.
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.
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.
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.
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.
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.
58: Zimmermann, HJ, Lewis, JH. Chemical and toxin-induced liver disease. Gastroenterol. Clin. N. Am. 1995; 24: 739.
59: Larrey, D.Hepatotoxicity of herbal remedies. J. Hepatol. 1997; 26: 4754.
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.
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.
62: Mowat, AP. Biliary disorders in childhood. Semin. Liver Dis. 1982; 2: 271–81.
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.
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.
65: Huxtable, RJ. The myth of beneficient nature: the risks of herbal preparations. Ann. Int. Med. 1992; 117: 165–6.
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