by Rachèle Teplier
The common name comfrey (Symphytum officinale L.), as many of its vernacular names, comes from its traditional use for bone healing. This common garden plant has an impressive range of medicinal uses taken internally and externally in different forms, for the treatment of a variety of diseases. However, the mode of therapeutic actions, at the molecular level, is not completely known and rigorous scientific evidences for its efficacy are still required.
The medicinal uses of comfrey have become controversial since the identification of its pyrrolizidine alkaloids-content, substances known for their toxicity in humans. Consequently, numerous toxicity studies of comfrey have been carried out, but the latter are regarded as inconclusive. Pending the provision of sufficient evidence of safety, comfrey is therefore subjected to legal restrictions in Europe and other countries, in which oral applications are inadvisable and a limited pyrrolizidine alkaloids-content in topical products is recommended.
Finally, although there is no sufficient scientific validation of its therapeutic effects and safety, the use of comfrey (root) for the cutaneous treatment of sprains and bruises has been approved in the European Union, on the basis of its well-documented traditional use. Therefore, comfrey can be used externally in the modern therapy, for bruises and sprains and are available for over-the-counter.
|WARNINGS FOR POTENTIAL TOXICITY (pyrrolizidine alkaloids content) :
The name comfrey is used today for Symphytum officinale L., although in the past it referred to several species in the genus Symphytum. Indeed, Symphytum officinale, belonging to the Boraginaceae (Borage family), is the major comfrey species of medicinal interest, among the 25 species of Symphytum. The other Symphytum species are rather used as forage plants, green manure and vegetable plants (e.g Russian comfrey – Symphytum x uplandicum Nyman) (Fell and Peck, 1968; Mei et al., 2010; Frost et al., 2013).
Comfrey (Symphytum officinale L.) is an invasive perennial herb which grows up to 90 cm / 3 feet in height. It is characterized by its long thick-hairy leaves with narrow ends, and its bell-like white, blue, yellowish to red-violet flowers (depending on the variety), blooming from May to July (Figures 1,2,3). Its deep spindle-shaped branched roots, black on the outside and white on the inside (Figure 4), are borne by a voluminous rhizome, which is an underground stem. Only the roots, rhizome and the leaves (dried or fresh) are the parts used medicinally (Cupp, 2000 ; Thomson Healthcare, 2007 ; Barceloux, 2008). Besides, the leaves are often used as a garden organic fertilizer, either as green manure or as an ingredient of compost. Indeed comfrey, with its taproot up to 3 m in length, is rich in a variety of nutrients (Wilkinson, 2003). In passing, these latter botanical features should be carefully considered in order to avoid a common misidentification with foxglove species (Digitalis spp.), which is well-known for its toxicity (especially on the heart – cardiotoxicity).
Native to Europe and Asia, comfrey now grows as a wild and common garden plant in all temperate regions of the world including Australia, North America. It is widespread throughout Ireland and Britain on riverbanks, ditches and it is often cultivated (Wichtl et al., 2004). In fact, comfrey thrives in rich moist soil in full sun, partial or heavy shade. It can not only be grown from seed but also by root division in which the mature plant is divided into smaller sections and both the new and the mature plant are replanted (Figure 4). However, comfrey is challenging to eradicate once established, due to its deep roots (Chevallier, 2001).
Traditional and Modern Uses
Comfrey has been used as a herbal medicine for more than 2000 years and the use of its root has a long-lasting tradition (Rode, 2002 ; Staiger, 2013). Indeed, around 200 AD, the Greek physician Disocorides described the medicinal uses of comfrey in his book Materia Medica, and coined the genus name Symphytum from the Greek word syuphuo, meaning « make to grow together ». In the Middle Ages, comfrey became widely popular for healing broken bones in the form of an external poultice and began to receive nicknames such as boneset, knitbone and knitback (Cupp, 2000).
Since then, comfrey has had an impressive expanded record of medicinal uses. On the one hand, both comfrey leaves and roots have been applied topically, in the form of extracts, ointments or poultices (Figure 6), for the treatment of wounds, joint disorders, bruises, sprains, pulled muscles and ligaments, inflammations, haemorrhoids and bone fractures (Frost et al., 2013). Interestingly, comfrey is distinguished as being one of the few specific medicinal plants used for treating bone disorders in most traditional European herbal medicine systems (Heinrich and Jäger, 2015). On the other hand, besides being considered for its nutritional value (source of protein and vitamin B12), comfrey has also been taken orally to treat gastritis, gastroduodenal ulcers and lung congestion, in the form of infusions and extracts (Roeder, 1995; Cupp, 2000; Mei et al., 2010).
Nowadays, in many countries comfrey is still used in local medicine as a topical treatment for bruises, burns, sprains and as an internal medicine (tea formulations or tablets). Ethnographic studies unveil similar uses worldwide (Mei et al., 2010; Frost et al., 2013). However, the popularity of comfrey has declined since the potential toxicity of pyrrolizidine alkaloids substances was emphasized (see « Toxicity » section). As a precaution, national regulatory agencies and international health organizations have developed restrictions or prohibitions for oral use of comfrey, throughout Europe (European Medicines Agency) and several countries (e.g USA, Canada, Australia, New Zealand). Consequently, all oral comfrey products, such as tablets and capsules, have been withdrawn and warning label against comfrey ingestion has been recommended for comfrey leaves and roots (Veitch et al., 2013).
Comfrey is currently under restriction in the UK. However, comfrey-based products (free of pyrrolizidine alkaloids or with a reduced pyrrolizidine alkaloids concentration) in semi-solid forms (creams, ointments), including homeopathic preparations, can be purchased over-the-counter for topical use. Comfrey is also available for internal or external use under prescription by physicians and qualified medical herbalists (Rode, 2002 ; Frost et al., 2013, British Pharmacopoeia 2014).
The constituents of Symphytum officinale include among others, complex sugars, which are part of an abundant mucilage in both comfrey roots and leaves, allantoin, rosmarinic acid, choline, triterpene saponins and tannins. Comfrey is also rich in many nutrients such as proteins, antioxidants and vitamins (including vitamin B12, which is unusual for a plant) (Rode, 2002).
In the late 1970s and 1980s, it has been revealed that comfrey contains also low levels (less than 1%) of the potentially toxic pyrrolizidine alkaloids of which the content is variably dependent on plant organs as well as plant species (Mei et al., 2010). Indeed, its concentration is the highest in roots while young leaves possess a higher concentration than mature leaves. Additionally, Symphytum officinale contains lower concentration of pyrrolizidine alkaloids than other species of comfrey such as Russian comfrey (Symphytum x uplandicum) (Barceloux, 2008; Frost et al., 2014).
- Experimental Data
Comfrey has been considered in traditional medicine for its anti-inflammatory, analgesic, anti-oedematous, astringent and wound-healing properties (Kučera et al., 2004 ; Araújo et al., 2012). In fact, studies, using oral and topical treatments of comfrey leaf extracts in rats, have disclosed a wound healing activity. In particular, topical treatments of comfrey leaf extracts have shown to be effective in treating excision wounds in rats, by increasing collagen deposition and controlling inflammatory processes (Goldman et al., 1985 ; Araújo et al., 2012).
Although, the key constituents of comfrey responsible for its therapeutic actions and mechanism have not been completely elucidated, the healing action is attributed mainly to allantoin which stimulates the regeneration of connective tissue, bone and cartilage, rosmarinic acid, an anti-inflammatory constituent, choline acting anti-oedemateously, tannins which are astringent and a mucilage showing anti-irritant, moisturizing and anti-inflammatory actions (Mei et al., 2010; Araújo et al., 2012; Frost et al., 2013).
- Clinical Data
Several evaluations attempted to assess the efficacy of cutaneous applications of comfrey species, alone or with any combination of herbs (commercial preparations), in the treatment of various muscle and joint complaints as well as skin conditions. Although based on modest evidence, the results of some clinical trials showed the superiority of topical use of comfrey preparations over placebo for reducing pain in ankle distortion, knee osteoarthritis (in case of short-term treatment), back pain and for speeding the healing of abrasion wounds. In particular, one clinical trial revealed a higher efficacy for topical application of comfrey compared to Voltaren® containing diclofenac (a topical gel used to treat joint pain) in treatment of ankle distortion (Koll et al., 2004 ; Predel et al., 2005 ; D’Anchise et al., 2007, Giannetti et al. 2010).
As a result of these trials, cutaneous applications might be effictive in the treatment of pain, inflammation and swelling in case of ankle distortion, back pain, abrasion wounds and knee osteoarthritis, though further rigorous assessments are still required. On the contrary, clinical studies are not conclusive regarding skin conditions due to inadequate evidence (Frost et al., 2013).
Nonetheless, when considering the potential therapeutic effects of comfrey constituents, note that the process of pyrrolyzidine alkaloids-depletion/removal for commercial comfrey preparations (assessed in the above clinical trials), might impact on the real efficacy of comfrey preparations (Andres et al., 1990). But, so far, there is no scientific evidence regarding the efficacy of pyrrolyzidine alkaloid-containing comfrey preparations.
In addition, other common traditional uses, such as, bone fracture healing, haemorrhoid treatment, are not evaluated yet (European Medicines Agency, 2011 ; Frost et al., 2013).
Pyrrolizidine alkaloids (PAs), are intrinsic components of comfrey and of a few widespread crop weeds, such as or tansy ragwort (Senecio jacobaea L.). These compounds are also found, for example, in coltsfoot (Tussilago farfara L.) Due to the presence of PAs, as environmental toxicants and contaminants, the ingestion of some PAs-plants has been implicated in accidental human and livestock (on a plant–based diet) poisonings, in various countries throughout the world (e.g Africa, India, Afghanistan, former URSS). PAs have been found toxic to the liver and lungs in humans. Accordingly, comfrey, which is the industrially most important pyrrolizidine alkaloid-containing plant, has given rise to safety concerns (De Smet et al., 1992 ; Prakash et al., 1999 ; Barceloux, 2008; Jedlinszki et al., 2016).
- Animal Experiments
The restrictions on the internal use of comfrey (Symphytum spp.) are essentially based on animal experiments (usually rats), in which comfrey has been found to induce liver damage, including hepatic tumour development (Mei et al., 2010). Although the precise mechanism of toxicity is unclear, PAs were suggested to be the main active constituents responsible for tumour induction in rodents (Mei et al., 2010). Therefore, comfrey has been classified hepatotoxic and as a potentially carcinogen in humans.
Nevertheless, there is high variability of toxicity among animal species in these experiments due to variable and sometimes poor experimental design (e.g use of different species of comfrey possessing different levels of PAs ; administration large doses of PAs isolated or from comfrey leaves and roots) and the use of inappropriate animals models (e.g pigs, chickens, and rats are much more sensitive than mice and sheep), among others (Rode, 2002). Besides, there is to date no direct evidence with regard to the association between the risk of cancer and the ingestion of PAs, in humans (Prakash et al., 1999).
- Human Data
In humans, outside of case reports of toxicity due to misidentification with foxglove (Digitalis spp.), only five cases of liver failure, manifesting primarily as hepatic veno-occlusive disease (i.e blockage of hepatic veins leading to the death of liver cells), were associated with long-term comfrey ingestion, in North America and Europe. However, crucial imprecisions of these case-reports might involve other causes of toxicity. The amount and duration of comfrey intake, the initial health and nutritional status, as well as the potential concurrent use of plants contaminated or containing PAs, increase the likelihood of hepatic veno-occlusive disease development. Besides, it has been reported that PA-poisoning in humans is most commonly a consequence of consumption of plants other than comfrey (Bruneton, 1999 ; Rode, 2002; Vithayathil et al., 2016).
Overall, there is a lack of rational evidence in support of the acute toxic effects of comfrey ingestion (chronic liver disease, cancer). Additionally, clinical trial have not been carried out. Despite a long history of oral use, further rigorous research is, therefore, needed to clarify the long-term health hazard of the ingestion of comfrey leaves and roots (Barceloux, 2008).
Cutaneous application of comfrey is of less concern than oral ingestion. But surprisingly, only rudimentary evaluations concerning the safety of PAs absorbed through the skin exist, as noted below :
- Animal Experiments
In rats, the dermal absorption of PAs obtained from comfrey is reported to be low, when compared to gastrointestinal absorption. It was concluded that an occasional external use of comfrey preparations should not be hazardous (Brauchli et al., 1983).
- Human Data
Studies in humans investigated the tolerability of cutaneous applications from commercial preparations of comfrey which are depleted of or PA-free. Generally, in adult patients, no adverse effects have been reported in association with cutaneous use of comfrey (Koll et al., 2004 ; Predel et al., 2005 ; Giannetti et al. 2010). However, there is insufficient data with regard to the cutaneous use in children and adolescents under 18 years of age (European Medicines Agency, 2015).
PAs from comfrey appear thus not to be of clinical significance when using commercial topical products of comfrey in which the amount of PAs has to be specified. Indeed, a limitation of maximum 0.35 microgram of PAs per day and per person has been recommended by the European Medicine Agency (European Medicines Agency, 2015).
Regarding the safety of PA-containing comfrey preparations, there is very little rigorous evidence (Frost et al., 2013).
In summary, further stringent safety and efficacy evaluation of the use of comfrey is needed, including special populations (e.g neonates, children, elderly) as well as PA-containing preparations reflecting much more human comfrey consumption (Frost et al., 2013; European Medicines Agency, 2015). However, one should emphasize that possible toxic effects on the liver still exists and therefore caution regarding comfrey use is recommended as indicated in the following section.
Cautions and Risks Interactions
Comfrey is contraindicated for cutaneous application to broken skin or open wounds and its use is restricted for no longer than 10 days. Besides, comfrey must not be taken by mouth due to its potentially toxic PAs content.
In view of the lack of safety evidence, pregnant and breastfeeding women should not use comfrey as well as children and the elderly (Veitch et al., 2013).
Otherwise, comfrey is generally considered safe to use on the unbroken skin for adults aged 19 years and older without medical supervision. (Veitch et al., 2013 ; European Medicines Agency, 2015).
There are no known scientific reports of interactions between comfrey and conventional or herbal medications, although comfrey preparations may interact with medicines administered concurrently, particularly those with similar or opposing properties (Barnes et al., 2007)
On a European level, the European Medicines Agency (London) concluded, on the basis of the well-documented traditional use of comfrey, that comfrey root can be used for the relief of symptoms of minor sprains and bruises. In other words, although there is insufficient evidence from clinical trials, as mentioned above, the effectiveness of cutaneous preparations of comfrey is plausible and there is evidence that they have been safely used in this way for at least 30 years (European Medicines Agency, 2015).
Asides from its medicinal properties, comfrey remains a fantastic source of organic fertilizer for gardens and crops.
In this essay we do not to advise or recommend herbs for medicinal or health use. This information is intended for educational purposes only and should not be considered as a recommendation or an endorsement of any particular medical or health treatment.
The use of any such product should be based on the appropriate advice of a health care professional or based on the information available in the patient information leaflets (i.e. for THR products)
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