Is it safe to use medicinal comfrey leaves or roots?

INTERNALLY consuming REGULAR /EXCESSIVE amounts of comfrey may cause liver / kidney damage 

To be safe, anyone with serious liver or kidney disease or taking hepatotoxic drugs should not use comfrey internally

The U.S. FDA warns that REGULAR consumption of LARGE amounts of comfrey tea, pills, root powder and/or extracts can lead to sinusoidal obstruction syndrome (SOS)(formally called hepatic veno-occlusive disease.  Potentially, this is a fatal form of liver damage caused by drugs /toxins, which can trigger fibrosis by altering DNA), and/or similar kidney cell damage.   In the U.S., comfrey- pepsin capsules are a likely source for concern;

Comfrey contains several potentially toxic UNsaturated pyrrolizidine alkaloids (uPAs) (saturated PAs are NON- toxic).   Including symphytine, echimidine, symglandine and lycopsamine.  uPAs are present in the plant families: Boraginaceae (E.g. Symphytum offinale (comfrey), Borago offinales (borage)),Fabaceae and Asteraceae (e.g. summer ragwort, gravel root, boneset, butterbur and coltsfoot), as part of their defense mechanism. If the liver's normal detoxification pathways are compromised or overwhelmed (e.g. by high dose uPAs), then uPA's are metabolized by the cytochrome P450 enzymes into highly toxic pyrrole metabolites with alkylating properties that can damage hepatic endothelial cells and can lead to SOS. Similarly, pyrrole can damage kidney cells. Damage can accrue slowly, silently and cumulatively with low- level comfrey consumption. Pyrrole can be broken down in the liver by glutathione and glutathione S- transferase enzymes in the liver

Liver injury is typically seen 1- 2 months after regular, EXCESSIVE comfrey consumption.   Beginning with right upper quadrant pain, nausea and fluid retention/weight gain, which is followed by jaundice. Infants seem to be particularly susceptible.  It is noted that as of 2015, studies have only shown association, and not causation, of comfrey PA's with liver toxicity. An inference is made that comfrey must cause toxicity, because PA's in other herbs, such as senacio, have shown causal liver toxicity.

What are the  risk factors for  uPA-associated damage?

-   Family history.   SOS, liver cirrhosis, pulmonary hypertension and right heart failure

-   Poor liver health.   History of infection, alcohol abuse

-   Children 1- 14.   Even after consideration of lower body weight

-   Babies / fetuses.   Due to higher copper levels in their livers

-   Pregnant / lactating mothers.   uPAs cross placental barrier, show up in milk

 -  Regular honey consumption.    May provide chronic low- dose of uPAs if bees visited PA- containing plants;

-   Concurrent use of certain herbs.  E.g. Hypericum perforatum (St John's Wort) / medications that induce CYP450 metabolic pathway

-   Low glutathione levels.   Possibly caused by high alcohol intake, low dietary sulfur / protein / selenium or genetic factors

Alkaloid Content of comfrey

Varies according to different studies - but generally PAs vary by:

 - Species - and even by  Individual plant; more prickly species (E.g. Prickly, Russian) contain more PAs  than less hairy leafed species.

- Growth state - age of plant; young leaves have higher concentration than older leaves; Small leaves of S. x Uplandicum found to have 16- fold increase over larger leaves. Mattocks AR (1980) Toxic pyrrolizidine alkaloids in comfrey Lancet 2 1136 - 7

- Plant part - roots have ~10 times more PAs than stems, flowers, leaves (Roitman 1981); highest concentration in small young roots, extreme exodermis and rhizome center.

- Time of harvesting and location

PAs convert to N- oxides, which forms are also toxic and not always counted in studies - estimated to be 7 times PA count

PAUL M. RIDKER, SEITARO OHKUMA, WILLIAM V. McDERMOTT, CHARLES TREY, and RYAN J. HUXTABLE,  Hepatic Venocclusive Disease Associated With the Consumption of PyrrolizidineContaining Dietary Supplements,  (1985) GASTROENTEROLOGY;88:1050- 4

A high concentration of symphytine is present in tea as its more soluble N- oxide - these derivatives could be reduced in vivo to their native PA and subsequently metabolised to the hepatotoxic pyrrole.

Analysis of herbal teas made from the leaves of comfrey (Symphytum officinale): Reduction of N- oxides results in order of magnitude increases in the measurable concentration of pyrrolizidine alkaloids (2004) Public Health Nutrition 7(7):919- 24

Unsaturated PAs are both water- and alcohol- soluble - and so can be found in teas and tinctures

Echimidine (likely the most toxic PA in comfrey) - in prickly and Russian comfrey, and ~25% of tested samples of Common comfrey.

Jaarsma, T.A., et al., Chemotaxonomy of the Symphytum officinale agg. (Boraginaceae). Plant Systematics and Evolution, 1989. 167(3- 4): p. 113- 128.Ref