Comfrey Central - A Clearinghouse for Symphytum Information





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General Information about Pyrrolizidine Alkaloids (PAs)

PAs in Comfrey

Review of Comfrey and Related Research

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In Vitro Studies

Table 5: In Vivo Studies
Test AnimalTest SubstanceDoseFrequencyEstimated equivalent dose of dry weight comfrey for 60kg human (a)ResultsRef
Male Rats 1-1.5 months oldSymphytine (i.p.)13mg/kgtwice weekly for 4 weeks and then once a week for 52 weeks. (Experiment ran 21 months)7 - 1040kg leaf (b) or 0.35 - 52kg leaf (c)liver cell adenoma: 1 rat out of 20
herangioendothelial sarcomas of the liver: 3 rats out of 20
megalocytosis and proliferation of oval cells and endothelium of the sinusoids
[81]
Male rats (n=3)Echimidine20mg/kgthrice weekly for 136 daysdose is about 3 to 4.5 times dose reported for symphytine study above (d)limited megalocytosis of the midzone and periphery of the lobule[85]
Male and Female rats 1-1.5 months oldLeaf% of diet
33%
33%
16%
8%

for 480 days
for 600 days
for 600 days
for 600days

0.5kg (1lbs)(e)

0.24kg (0.5lb)
0.12kg (0.25lb)
incidence of liver tumors (f)
26%
58%
33%
4%
[89]
Male and Female rats 1-1.5 months oldRoot% of diet
8%
4%/2%/1%
4%/0.5%/0%
2%/0.5%/0%
1%/0.5%/0%
variable time courses, >179 days with first diet composition 0.12kg (4oz)
0.06kg (2 oz)

0.03kg (1 oz)
0.02kg (0.5 oz)
incidence of liver tumors (f)
86%
43%
33%
43%
80%
[89]
Male Rats (140g)Symphytum leaf% of diet
5%
10%
30%
21 days 0.3kg (0.67 lbs)
0.6kg (1.3lbs)
1.8kg (4lbs)
at 30% comfrey there was a significant decrease in daily weight gain at 10% and 30% comfrey (and 30% alfalfa) significant increase in Aminopyrine-N-demethylase activity. No changes in Glutathione S-transferase or Epoxide hydrolase at any feeding levels. [90]
Rats 2 weeks old Total Symphytum PA (i.p.)284 mg/kgonce19kg -130g leaf (42lbs - 4.5oz) or 2.8kg - 34g root (6lbs - 1.2 oz)peracute (non-hepatic) deaths[65]
Rats 2 weeks old Total Symphytum PA (i.p.)142 mg/kgonce9.5kg - 65g leaf (21 lbs - 2.2oz) or 1.4kg - 17g root (3lbs - 0.6oz)Temporary distress, no histological liver damage evident when rats killed 4 weeks later.[65]
Male and female rats 2 weeks oldTotal Symphytum PA (i.p.)71 mg/kgthrice weekly until death at 3-4 weeks4.7kg - 32g leaf (10lbs - 1oz) or 0.7kg- 8.5g root (1.6lbs - 0.3oz)death due to severely impaired liver function but mild histological damage[65]
Male and female rats 2 weeks oldTotal Symphytum PA (i.p.)17.8 mg/kgthrice weekly for 3 weeks1.2kg - 8g leaf (2.6lbs - 0.3oz) or 180g -2g root (6oz - 0.07 oz)reduced liver function (liver histology not checked)[65]
Male and female rats 2 weeks oldTotal Symphytum PA (i.p.)17.8 mg/kgthrice weekly for 9 weeks1.2kg - 8g leaf (2.6lbs - 0.3oz) or 180g -2g root (6oz - 0.07 oz)megalocytosis[65]
Male and female rats 2 weeks oldTotal Symphytum PA (i.p.)8.9 mg/kgthrice weekly for 3 weeks(0.6 kg - 4g leaf) (1.3 lb - 0.1 oz) or 89g - 1g root (3oz - 0.04oz)reduced liver function (liver histology not checked)[65]
Rats young adultsTotal Symphytum PA (oral)200mg/kgSingle dose13kg - 91 g leaf (29lbs -3 oz) or 2kg - 24g root (4.4 lbs - 0.9 oz)All rats showed evidence of liver damage that was dose dependent.[76]
Rats young adultsTotal Symphytum PA (oral)100mg/kgthrice weekly for 3 weeks6.7kg - 45g leaf (15 lbs - 1.6 oz or 1kg - 12 g root (2.2 lbs - 0.4oz)All rats showed evidence of liver damage that was dose dependent.[76]
Rats young adultsTotal Symphytum PA (oral)50 mg/kgthrice weekly for 3 weeks3.3kg - 23g leaf (7.3 lbs - 0.8oz) or 0.5kg - 6g root (1 lb - 0.2 oz)All rats showed evidence of liver damage that was dose dependent.[76]
Rats young adultsTotal Symphytum PA (oral)50mg/kgonce a week for 6 weeks3.3kg - 23 g leaf (7.3 lbs - 0.8oz) or 0.5kg -6g root (1 lb -0.2 oz)All rats showed evidence of liver damage that was dose dependent.[101]
(a) Ranges calculated based on data from table 3: leaf contains between 15 and 2200g total alkaloids./g and root contains between 100 and 83\230g total alkaloids/g.
(b) Given 5% of comfrey PA are symphytine [65]
(C) Alternately if all alkaloids have equivalent toxicity to symphytine.
(d) Assuming echimidine is one half to a third of the concentration of symphytine [82].
(e) Assuming rat eats 10g/day and weighs 100g
(f) Proliferation of the intrahepatic bile duct, megalocytosis, hyperplastic nodule or liver cirrhosis was encountered frequently, even in rats without tumors. 2004 Dorena Rode