For centuries, comfrey has garnered much notoriety as an effective healing agent. The ancient Greek’s knew of its purported medicinal properties, as did many societies within the time period of the Middle Ages. There were many stark contrasts regarding the time, location, medicinal beliefs, and herbal knowledge of persons living in these eras. Regardless of these differences, scientists now know that comfrey was consistently used as an internal and external remedy for a wide range of physical ailments. In fact, the herb’s Latin name is derived from the Greek term “sympho,” meaning to unite, or to grow together. It is no wonder then why comfrey it often termed “Knitbone,” or “Boneset.”
Comfrey’s application in the treatment of wounds, sprains, and broken bones, may be well justified. Recent study has pointed to its many phytochemicals as the primary source for this effect. It is postulated that allantoin (a protein), mucilage (a gelatinous material), rosmarinic acid (antioxidant), and caffeic acid are among the most important constituents responsible for the advanced anti-inflammatory and tissue regenerating actions of comfrey.  Potentially toxic pyrrolizidine alkaloids, or PAs, and mucopolysacharides are also present in this plant, however, their therapeutic relevance remains unknown and the consumption of the PAs can be quite harmful.
In association to the abovementioned medicinal constituents, comfrey also contains numerous vitamins, minerals, and proteins. These include, and are not limited to; vitamins A, C, B1, B2, and B3, calcium, potassium, iron, magnesium, mucilage, copper, zinc, and selenium.  It’s protein content has been found to be comparable to that of legumes.  Because of this high nutritional content, a number of herbalists use comfrey for targeted oral applications, ignoring the possible alkaloid toxicity at hand.
Oral forms of comfrey are used for supposed antibacterial and expectorant actions. Dried comfrey may also be used to assist in gastrointestinal (GI) disorders, diarrhea, and ulcerative conditions. Detractors of PA toxicity often dispel this notion by pointing to the historical significance of this herb. They often argue that other common foods have been shown to be equally as poisonous when taken in large amounts, such as; teas, almonds, radishes, mustard, etc.  Regardless of this argument, its internal usage remains ill advised.
Nutritional supplements which contain oral forms of comfrey are prohibited in the United States and several other countries. The U.S. Federal Trade Commission (FTC), and Food and Drug Administration (FDA), asked retailers to pull comfrey-containing oral supplements off the market in July 2001.  This effort was the end result of scientific study indicating that certain compounds in the herb, primarily alkaloids, could produce liver damage and may even be carcinogenic.  (See Toxicities) All external products, which allow comfrey to be readily absorbed through skin, must now provide label warnings as well.
Due to the possible toxicity associated with the ingestion of comfrey, it is not recommended for internal use unless administered by a medical practitioner. Topical preparations of comfrey are still widely available and are considered safe when taken in accordance with label instructions. The most popular and recommended topical application for comfrey is ointment, which contains a 5 - 20% standardized extract from comfrey leaves. This percentage of extract is also included in popular chapped-lipped ointments and diaper creams. Other forms of comfrey are delivered via poultices, liniments, and teas made from the dried herb.
Despite its reputed uses for various gastrointestinal disorders, clinical application into the usage of comfrey remains limited. This limitation of information is caused by both the restricted methods of comfrey supplementation, and the ever-increasing fear of a possible comfrey-related toxicity. As comfrey is only available for supplementation by means of topical delivery methods, the only practical use for comfrey-containing products are within the treatment of wounds and promotion of tissue healing/regeneration. [7, 8]
Although unsubstantiated, the chemical compounds allantoin and rosmarinic acid are often credited with comfrey’s wound healing and tissue regenerating properties. Allantoin is actually a natural nutrient found in the milk of nursing mothers and has been shown to have a pronounced affect on cell multiplication rates; an important component of the growth process. Comfrey ointments containing high levels of allantoin and rosmarinic acid have been used to treat burns, sores, wounds, and inflammation caused by broken bones and bruising.
In one particular double-blind study, external preparations were used to treat bruises, ankle distortions, and sprains. Patients received either 2 grams of comfrey extract ointment, or an ointment containing no comfrey extract, administered four times daily for an average duration of 7 to 9 days. Upon completing the study, the comfrey group exhibited greater efficacy in areas of joint mobility and flexion. Researchers also indicated that comfrey may be an effective agent for the control of pain and swelling associated with different types of soft tissue injuries. 
It is still unknown how much comfrey is actually needed to treat certain soft tissue traumas and inflammatory conditions. It is equally difficult to determine the amount of phytochemicals absorbed through the skin from various comfrey-containing supplements. This makes establishing a tolerable or recommended dosage near impossible. In the United States, it is widely agreed that comfrey should be taken in accordance with the individual manufacturers instructions, and not be applied for more than a period of 10 days at a time. There is also some concern regarding the amount of topical comfrey administered in one year. A good rule of thumb is to limit usage to less than two months total, per year.
In European countries, comfrey preparations are rigorously monitored for the varying amounts of PAs contained in each product. Germany has set a limit of 1 microgram of pyrrolizidine alkaloids per day when comfrey is taken for internal healing. When it is applied to the skin, the maximum value of PAs allowed increases to nearly 100 micrograms per day. The U.S., unlike Europe, does not routinely evaluate the potency of commercial products that contain comfrey.
Although not all pyrrolizidine alkaloids are harmful to humans, the amounts found in various comfrey species may prove extremely toxic, and possibly cancerous.  Comfrey poisoning has proven extremely rare in controlled studies. Experts still agree that it should never be ingested, or applied to broken skin. Laboratory studies have focused on a specific pyrrolizidine alkaloid found in comfrey, named echimidine. Elevated levels of this highly toxic compound have been found in both “prickley,” and “Russian” comfrey. Scientists have concluded, through various mammalian study, that the consumption of certain PAs found in comfrey may prove extremely detrimental to the liver. 
Taking comfrey in high doses, or low doses over an elongated period, may result in the progression of a adverse condition known as HVOD, or hepatic veno-occlusive disease.  Hepatic veno-occlusive disease is characterized by the blockage of veins and constriction of blood vessels of the liver, resulting in impaired liver function. This impairment causes PAs to continue damaging other delicate tissues located throughout the body, possibly leading to pulmonary hypertension.  The personal administration of comfrey, in any form, remains inadvisable for children, the elderly, and pregnant and lactating women.
In addition, side effects reported from long-term use of topical comfrey include:
- Loss of Appetite
- Increasingly tender abdomen/abdominal pain
Persons taking comfrey-containing products for long durations should be aware of the signs and symptoms of liver damage. Individuals with liver damage often exhibit signs of:
- Constant widespread itchiness
- Vomiting and Diarrhea
- Pain, with accompanied swelling, in upper right area of abdomen
- Yellowing of skin or eyes (known as jaundice)
- Extreme lethargy
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