Symphytum

Comfrey/Drug Interactions:

  • GeneralGeneral: Oral products containing comfrey leaf in combination with other ingredients were found to have lower total levels of alkaloids compared with bulk comfrey root or leaf (41).
  • Aminopyrine N-demethylase metabolized agentsAminopyrine N-demethylase metabolized agents: In animal research, oral comfrey (Symphytum officinale) increased the activity of the hepatic enzyme, aminopyrine N-demethylase (64).
  • AnalgesicsAnalgesics: In human research, topical comfrey provided analgesic effects and reduced analgesic consumption (40; 39; 59; 1; 2; 3; 5; 6; 4; 21).
  • AntifungalsAntifungals: Extracts from the leaves of comfrey inhibited the germination of Erysiphe graminis conidia and uredospores of Puccinia graminis, resulting in diminished powdery mildew infection of plants (8). It is unclear whether comfrey has clinical antifungal effects.
  • Anti-inflammatory agentsAnti-inflammatory agents: In human research, topical comfrey provided anti-inflammatory effects (3; 1; 2; 6; 4).
  • AntineoplasticsAntineoplastics: In vitro, comfrey had carcinogenic activity (52; 63; 55).
  • Cytochrome P450 3A4-inducing agentsCytochrome P450 3A4-inducing agents: In vitro, agents that induce CYP3A4 increased the conversion of compounds in comfrey to toxic metabolites (12).
  • Hepatotoxic agentsHepatotoxic agents: According to case reports and animal studies, oral or topically absorbed comfrey had additive adverse effects on the liver when used in combination with hepatotoxic medications (32; 33; 34; 35; 36; 37).

    • Comfrey/Herb/Supplement Interactions:

  • GeneralGeneral: Oral products containing comfrey leaf in combination with other ingredients were found to have lower total levels of alkaloids compared with bulk comfrey root or leaf (41).
  • Aminopyrine N-demethylase metabolized agentsAminopyrine N-demethylase metabolized agents: In animal research, oral comfrey (Symphytum officinale) increased the activity of the hepatic enzyme, aminopyrine N-demethylase (64).
  • Analgesic agentsAnalgesic agents: In human research, topical comfrey provided analgesic effects and reduced analgesic consumption (40; 39; 59; 1; 2; 3; 5; 6; 4; 21).
  • AntifungalsAntifungals: Extracts from the leaves of comfrey inhibited the germination of Erysiphe graminis conidia and uredospores of Puccinia graminis, resulting in diminished powdery mildew infection of plants (8). It is unclear whether comfrey has clinical antifungal effects.
  • Anti-inflammatory agentsAnti-inflammatory agents: In human research, topical comfrey provided anti-inflammatory effects (3; 1; 2; 6; 4).
  • AntineoplasticsAntineoplastics: In vitro, comfrey had carcinogenic activity (52; 63; 55).
  • AntioxidantsAntioxidants: In vitro, a water-soluble hydroxycinnamate-derived polymer (>1000kDa) from Symphytum asperum Lepech reduced the diphenylpicrylhydrazyl radical and inhibited the nonenzymatic lipid peroxidation of bovine brain extracts (18). Superoxide anion generation was also reduced. In vitro, topical formulations including Symphytum officinale showed some antioxidant and free radical scavenging activities (10).
  • Cytochrome P450 3A4-inducing agentsCytochrome P450 3A4-inducing agents: In vitro, agents that induce CYP3A4 increased the conversion of compounds in comfrey to toxic metabolites (12).
  • LicoriceLicorice: In theory, combination use of topical licorice (Glycyrrhiza glabra) and comfrey may offer additional anti-inflammatory effects.
  • Ginkgo bilobaGinkgo biloba: In theory, combination use of topical Ginkgo biloba and comfrey may offer additive anti-inflammatory effects.
  • Hepatotoxic agentsHepatotoxic agents: According to case reports and animal studies, oral or absorbed comfrey had additive adverse effects on the liver when used in combination with hepatotoxic medications (32; 33; 34; 35; 36; 37).
  • PokeweedPokeweed: In vitro, watery extracts of both pokeweeds (Phytolacca americana) and comfrey precipitated human glycoproteins, agglutinate sheep red blood cells (SRBC) and stimulated lymphocyte adherence to nylon fibers (65).
  • Pyrrolizidine alkaloid-containing herbsPyrrolizidine alkaloid-containing herbs: In theory, orally or topically absorbed comfrey, in combination with other pyrrolizidine alkaloid-containing herbs may increase total levels of pyrrolizidine alkaloid consumed, which increases the risk for toxicity. Herbs containing pyrrolizidine alkaloids include alkanna, borage, butterbur, coltsfoot, forget-me-not, gravel root, hemp agrimony, hound's tongue, lungwort, and Senecio spp.
  • RosemaryRosemary: In vitro, rosemary (Rosmarinus officinalis L.) extracts and comfrey extracts both induced glutathione (GSH) adducts (52).
  • SassafrasSassafras: In vitro, sassafras (Sassafras albidum Nutt.) extracts and comfrey extracts both induced glutathione (GSH) adducts (52).
  • Uterine tonic agentsUterine tonic agents: In vitro, comfrey had uterine tonic effects (17). Other uterine tonic agents include chamomile (Matricaria chamomilla L.), pot marigold calendula (Calendula officinalis L.), cockscomb (Celosia cristata L.), plantain (Plantago lanceolata L. and Plantago major L.), shepherds purse (Capsella bursa pastoris L.), and St.-John's wort (Hypericum perforatum L.) (17).

    • Comfrey/Food Interactions:

  • CerealCereal: Contamination of cereals is a source of pyrrolizidine toxicity in Jamaica, India and Afghanistan (12).

    • Comfrey/Lab Interactions:

  • Aminopyrine N-demethylaseAminopyrine N-demethylase: In animal research, comfrey increased activity of aminopyrine N-demethylase (64).
  • Glutathione (GSH)adduct formationGlutathione (GSH)adduct formation: In vitro, comfrey extracts induced GSH adducts (52).
  • Leukocyte infiltrationLeukocyte infiltration: In an animal study, comfrey extract (Symphytum officinale L.) inhibited leukocyte infiltration (66).
  • Liver function testsLiver function tests: According to a review, comfrey increased alkaline phosphatase, aspartic acid transaminase, alanine aminotransferase, bilirubin, gamma glutamyltransferase, and lactate dehydrogenase levels (42; 38).
  • Liver pathologyLiver pathology: In animal research, comfrey caused vascular congestion, mild zone 3 necrosis, and loss of definition of hepatocytes cellular membranes (48). In the study, ultra structural abnormalities included endothelial sloughing, the loss of hepatocyte microvilli, and florid bleb formation on the sinusoidal borders of hepatocytes. Blebs were shed into the space of Disse and extruded to fill sinusoidal lumina. Platelets were also found where blebs were formed. Late damage in collagenization of Disse's space was also observed. In a separate animal toxicity study, liver pathology occurred, including swelling of hepatocytes and hemorrhagic necrosis of perivenular cells (49). There was also a loss of sinusoidal lining cells with disruption of sinusoidal wall. Sinusoids were filled with cellular debris, hepatocyte organelles and red blood cells.
  • Pyrrolizidine alkaloidsPyrrolizidine alkaloids: According to secondary sources, blood levels of pyrrolizidine alkaloids may increase with comfrey consumption or use on wounds.
  • T lymphocytesT lymphocytes: In vitro, comfrey extract had an antimitotic effect on human T lymphocytes stimulated with phytohemagglutinin (PHA) (50).