Alkaloids comfrey

A dietary supplement may be safe when taken in the recommended doses but may become dangerous in higher doses. However, patients may develop side effects even when ingesting recommended doses. Adverse reactions may be due to allergic reactions, dietary supplements containing toxic substances, mis-identification of plant, mislabeling of plant, natural toxic substances such as pyrrolizidine alkaloids in comfrey, unnatural toxic substances such as heavy metals, or pesticides. 

Many herbal teas, comfrey Pyrrolizidine alkaloids, including intermedine, lycopsamine, and symphytine... 

Comfrey Internal digestive aid topical for wound healing Pyrrolizidine alkaloids, hepatotoxicity Avoid ingestion topical use should be limited to 4-6 weeks... 

Comfrey (Symphytum officinale) Uses Topical treatment of wounds, bruises, sprains, inflammation Action Multiple chemical components, allantoin promotes cell division, rosmarinic acid has anti-inflammatory effects, tannin possesses astringent effects, mucilage is a demulcent w/ anti-inflammatory properties, pyrrolizidine alkaloids cause hepatotox Available forms Topical application w/ 5—20% of herb applied on intact skin for up to 10 d Contra Do not take orally d/t hepatotox, do not use if PRG or w/ lactation Notes/SE N/V, exfoliative dermatitis w/ topical use Interactions T Risk of hepatotox W/ ingestion of borage, golden ragwort, hemp, Petasites EMS None... 

Some herbal products are very toxic. Comfrey may be an effective treatment for bruises and sprains, but it contains pyrrazolidine alkaloids, which can cause severe liver damage. 

Russian comfrey (Symphytum x uplandicum Nyman) is widely recommended as a medicinal herb and an item of human diet. A previous investigation of this species led to the isolation of three alkaloids which were not fully characterized (cf. Vol. 7, p. 57). Culvenor and co-workers have separated eight pyrrolizidine alkaloids from the leaves of this perennial plant by counter-current distribution.21 The known alkaloids echimidine (51), symphytine (52), lycopsamine (53), and intermedine (54) were present. In addition, four new alkaloids, i.e. 7-acetyl-lycopsamine (55), 7-acetylintermedine (56), symlandine (57), and uplandicine (58), were characterized by spectroscopic methods, and by hydrolysis. The total alkaloidal extract caused chronic hepatotoxic effects in rats, and the authors... 

Symphytum officinale (black wort, boneset, bruise wort, comfrey, knitback, knitbone, slippery root) contains pyrrolizidine alkaloids, such as lasiocarpine and symphytine, and their N-oxides, and has repeatedly been associated with hepatotoxicity. 

Comfrey products have been withdrawn from the market in several countries, including the USA and the UK. The German Federal Health Office has restricted the availability of botanical medicines containing unsaturated pyrrolizidine alkaloids (1,2). Herbal medicines that provide more than Img internally or more than 100 mg externally per day, when used as directed, are not permitted herbal medicines that provide 0.1-1 mg internally or 10-100 mg externally per day, when used as directed, may be applied only for a... 

Betz JM, Eppley RM, Taylor WC, et al Determination of pyrrolizidine alkaloids in commercial comfrey products (Symphytum sp.). 1 Pharm Sci 83 649-653,1994... 

Comfrey is a perennial herb used for the prevention of kidney stones nourishing and repairing bone and muscle and for the treatment of injuries such as burns and bruises. In Australia, comfrey is classified as a poison and its sales have been restricted in several regions. Many different commercial forms of comfrey are marketed, including oral and external products. Commercial comfrey is usually derived from the leaves or roots of Symphytum officinale (common comfrey). However, some products are also derived from Russian comfrey. Russian comfrey contains a very toxic pyrrolizidine alkaloid, echimidine, which is not found in common comfrey. However, common comfrey contains other hepatotoxic alkaloids, namely 7-acetylintermedine, 7-acetyllycopsamine and symphytine. The metabolites of these alkaloids are very toxic to the liver. Ridker et al. documented hepatic venocclusive disease associated with consumption of comfrey root. Long-term smdies in animals have also confirmed the carcinogenicity of comfrey in animal models. ... 

Commercial comfrey is usually derived from the leaves or roots of Symphytum officinale (common comfrey) (USP, 1998). However, some products are derived from Symphytum x uplandicum Nyman (Russian comfrey) or Symphytum asperum Lepech (prickly comfrey), which appear to be more toxic than common comfrey (Anonymous, 1998). Russian comfrey and prickly comfrey contain a very toxic pyrrolizidine alkaloid (PA) called echimidine that common comfrey does not contain (Tyler, 1994). Although common comfrey does not contain echimidine, it does contain other hepatotoxic PAs. These alkaloids include 7-acetylintermedine, 7-acetyllycopsamine, their unacetylated precursors, and symphytine (Tyler, 1993). 

An animal study supports Mattock s hypothesis. The absorption of comfrey through unbroken skin is very low and should not cause toxicity. A Swiss experiment with rats showed that 0.1-0.4% of a dermal dose of 194 mg of alkaloid A-oxides/kg (extracted from the roots of Polish S. officinale) was recovered in the urine 48 h later (Brauchli et al., 1982). The researchers noted that the orally ingested alkaloids showed up in the urine at 20-50 times the concentration of the alkaloids found in the urine after dermal administration. Of the dermally absorbed alkaloids, only a small amount was converted to the toxic free alkaloids. These researchers concluded that short-term dermal use of comfrey should not be dangerous. 

In 1994, Joseph Betz, an FDA pharmacognosist, analyzed the PA content of 11 products containing comfrey that were bought throughout the Washington, DC area. Of the 11 products purchased, 9 had measurable levels of alkaloids (Betz et al., 1994). The levels of alkaloids present in these products could provide an explanation of the hepatotoxicities attributable to comfrey seen over the last 30 yr. It is estimated that comfrey root tea can contain up to 26 mg of alkaloid per cup (Bach, 1989). Although the comfrey root contains a much higher amount of alkaloids than the comfrey leaves, teas made with comfrey leaves contain measurable amounts of alkaloids because PAs are water soluble (Betz et al., 1994). Case reports of hepatotoxicity associated with comfrey tea contradict proponents who claim that the tea is safe because the alkaloid content of the leaf is low, and the alkaloids are not water soluble. 

Mattocks A. Toxic pyrrolizidine alkaloids in comfrey. Lancet 1980 2 1136-7. 

Yeong ML, dark SP, Waring JM. The effects of comfrey derived pyrrolizidine alkaloids on rat liver. Pathology 1991 23 35-8. 

The level of alkaloids in Symphytum officinale (comfrey) at various stages of plant development has been investigated. The alkaloid content appears to be greatest in the aerial parts during flowering and in the roots at the end of fruit formation. The alkaloids identified include lasiocarpine and heliosupine N-oxide in the aerial parts, and viridiflorine, echinatine, and heliosupine IV-oxide in the roots.23... 

The stems and leaves of Lappula intermedia (Echinospermum intermedium), at the fruit-bearing stage of development, contain lasiocarpine (21) and two other alkaloids, which were not identified.29 In general, the alkaloid content is stated to be similar to that of Caucasian comfrey. 

It may be mentioned in passing that comfrey was cited as a folkloric herb with curative powers but it is not mentioned that toxic PAs are a component (e.g., in Hoffman, 1999, pp. 76,90). As for alkaloids, among the anticancer agents mentioned are the Vinca alkaloids used successfully against childhood leukania, and the alkaloids scopolamine and hyoscyamine that occur in the mandrake root (and in other plants, such as henbane). 

Nevertheless, Foster and Johnson emphasize that comfrey also contains toxic pyrrolizidine alkaloids (PAs), as documented in Chapter 6. Although PAs will help stop bleeding, the negative effects outweigh the beneficial, for comfrey has been found to cause liver damage and produce cancerous liver mmors. Despite its long history in herbal medicine, no clinical smdies have documented any positive effects attributable to comfrey. Many studies, however, have demonstrated its liver toxicity. 

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