Safety Issues Affecting Herbs
Usnea: an herb used in Western and Chinese medicine
Usnea (Chinese: songluo) is a common sight for anyone who walks in the woods. It is the green tangly mass that hangs down from the dead trunks and branches of trees, especially pine trees, sometimes called "old man's beard." The Chinese name refers to the pine tree (song) and the plant's appearance as a hanging plant (like a vine; luo) reminiscent of a fish-net (also luo). Botanically, it is a lichen: a symbiotic integration of a fungus with an algae. There are several species of Usnea with slightly different forms and colors; they belong to the general category of fruticose lichens, commonly called "hanging hair" lichens. The Usneas have a double filament, with an inner core of white to yellow, and an outer portion that is green to grey, the green is contributed by the algae's chlorophyll.
The appearance of usnea like a mass of cloth fibers immediately suggested itself to primitive people as a useful topical application to wounds and skin inflammation; it can be readily collected and pressed down to make a dressing (pictured right). This turned out to be a valuable application not just in terms of its structure, but also because usnea contains potent antibacterial components that will help prevent wounds from getting infected and, thereby, contributes to more rapid healing. As a topical antiseptic, it has been used recently in making sophisticated skin creams, vaginal inserts, and mouth washes. It has also been developed into a medicinal herb for internal use. In Europe, it is manufactured, for example, into lozenges to treat oral inflammation (which is basically a topical use, though the content is swallowed); in China, it is used to make decoctions in the treatment of bronchitis with profuse sputum and as part of herbal cancer therapy, particularly for thyroid cancers.
One of the main active ingredients of usnea is the bitter, yellow, polyphenolic acid called usnic acid (structure diagram, left) that makes up about 1% of the crude material. It is thought to protect the lichen from adverse effects of sunlight exposure and deter grazing animals with its bitter taste. Since its first isolation in 1844, usnic acid has become the most extensively studied lichen metabolite and one of the few that is commercially available. It is well known as an antibiotic substance (1) that is also found in many other lichens.
Usnic acid is primarily effective as an inhibitor of gram positive bacteria-including tuberculosis, staphylococcus, streptococcus, and pneumococcus. It functions as an antibiotic by blocking oxidative phosphorylation, an essential part of bacterial metabolism. Isolated usnic acid has been considered a potentially valuable therapeutic agent especially during the past 50 years, with research aimed not only toward broad antibiotic properties (against bacteria, fungi, amoebas, and viruses), but also anti-inflammatory action, analgesic action, and potential anticancer effects. In addition to usnic acid, usnea also contains other organic acids, including usnaric, thamnolic, lobaric and stictinic acids, all of which are present in small amounts and not well-studied.
Usnea has been used for a long time in Native American medicine, European medicine, and Chinese medicine. In all cases, topical applications are the leading ones, but there are also some internal uses mentioned, especially in China. In Oriental Materia Medica (2), usnea is listed with the phlegm-resolving herbs, with these properties noted:
Taste: bitter, sweet
Traditional Uses: cleanses lungs, resolves phlegm, controls bleeding, removes toxin
Applications: headache, ocular irritation, cough, profuse phlegm, malaria, scrofula, leukorrhea, functional bleeding, wound bleeding, carbuncle, toxic snake bite.
The herb is mentioned in formulas for treatment of thyroid cancer in modern China, as in the three formulas below relayed in Treating Cancer with Chinese Herbs (3).
All these formulas rely, for their effects, on the pair of seaweeds sargassum and laminaria, along with usnea as key ingredients for resolving "phlegm" masses. While these formulas are indicated for thyroid tumors, they might also be given for other swellings in the upper body where phlegm accumulation is thought to be a cause of masses according to the traditional Chinese medical system.
These formulas were administered during a limited historical period for applications in cancer therapy, prior to development of modern medical therapies in China, but probably after 1960.
Modern herbalists in the West promote use of usnea internally for treating infections, which is consistent with the known antibiotic actions of usnic acid, but also make claims of immune enhancing effects, though there is little or no support for this latter suggestion.
Usnea became known in certain circles as an aid to weight loss, partly based on the idea that its uncoupling of oxidative phosphorylation would cause cells to burn up excess energy stored in fats. The development of this application of the herb and its active constituent has been attributed to (or blamed on) the late Dan Duchaine, who heavily promoted steroids and steroid substitutes for use by body builders to gain muscle and lose fat. He suggested that usnic acid could substitute for dinitrophenol, a substance that functions as an androgen but is potentially quite dangerous. Duchaine had some products manufactured through a company called Syntrax Innovations. This company sold usnic acid in a product called "LipoKinetix." Although it has been said in some press reports that the sole ingredient was usnic acid (sometimes labeled as sodium usnate), the product is apparently a complex formulation that includes another potentially dangerous compound, phenylpropanolamine (PPA), and also contains caffeine, yohimbine hydrochloride, and diiodothyronine.
Recently, in Spring 2003, press reports appeared indicating that ingestion of usnic acid, as the suspect compound in LipoKinetix, caused liver failure (requiring liver transplant) that was complicated by cerebral edema in one individual who took the product, and liver damage in six other cases. The duration of ingestion for this adverse effect is just a few weeks. The first FDA warning appeared in 2001 and was updated in spring of 2002 (4), and formally reported in Annals of Internal Medicine at the same time (5). There may have been other cases of liver damage from this same product (6), based on retrospective studies.
Syntrax discontinued sale of the product, though usnic acid is sold under other names in copycat products, including Ab-Solution Plus and Lipoburn, though it may soon be withdrawn from those products as well. It is entirely possible that high doses of usnic acid taken for weight loss-compared to the amounts utilized for most traditional uses-or its combination with other ingredients or impurities in the supply contributed to the adverse effects. The underlying factors affecting individual consumers that might lead to an adverse reaction to usnic acid are not known. However, pharmacologists familiar with the action of usnic acid consider that its desired effect of uncoupling oxidative phosphorylation is also a potential cause of the liver damage. Aside from those presenting with liver failure, several product users complained of rashes that developed soon after starting the regimen (usnic acid is known for causing contact dermatitis), but many persisted in use of it due to apparent success in losing weight.
Since most traditional uses of usnea are for topical applications or for short-term therapies (e.g., for mouth inflammation or bronchitis), it is possible that regular ingestion of usnea is an aspect of the risk revealed by these new products, some of which are used for weeks on end. In Chinese medicine, although usnea has been listed as a medicinal herb for internal use since ancient times (mentioned in the ancient Shennong Bencao Jing, 7) it is not included in formulas that come down to us from ancient times, and is not routinely used in the Orient for internal use today.
Some pharmaceutical products that inhibit oxidative phosphorylation are also associated with liver failure in a small number of users. For example, tolcapone, a drug for Parkinson's disease, was withdrawn from the European market due to three cases of hepatic damage attributed to its use. It was thought that mitochondrial uncoupling of oxidative phosphorylation by tolcapone, and consequent impairment of energy production by hepatocytes, could be responsible for the observed effects (8). These adverse events may occur in those with heightened sensitivity to the mitochondrial reaction or by unusual patterns of drug metabolism, explaining their infrequent effects (9).
Based on the possibility that the desired effects of usnea and the adverse effects are due to the same mechanism, and because of the serious consequences of the adverse effects even if rare, it is advisable to avoid internal use of usnea until more is known. Topical applications should be safe because of the very limited absorption of usnic acid. It is used for fungal infections such as athlete's foot, vaginal infections (Trichomonas and Chlamydia), and infected wounds, and it is an ingredient in herbal deodorants. However, topically applied usnea or usnic acid can cause an allergic reaction (i.e., skin rash).
Usnic acid is found in many lichens, so there should be some caution in using the other lichens for internal medicine. As examples, parmellia has been used in Chinese medicine (called shier; rock ear) as a blood nourishing herb that is said to supplement the kidneys, benefit the vision, and promote diuresis. Parmellia contains usnic acid, but it is sometimes substituted by a fungus product (not a lichen) called Gyrophora esculenta, which does not contain usnic acid. In Western herbalism, Iceland moss (Cetraria icelandica) is used internally as a medicinal; though called a moss, it is actually a lichen. It is used for resolving coughs, and may have a similar action to that of usnea in terms of its treatment of cough with phlegm.
An additional problem associated with internal use of lichens is that they readily absorb heavy metals and retain them. These heavy metals may come from pollution in the atmosphere (previously, high levels of lead from vehicle exhaust was a significant concern, but lead has been removed from gasoline supplies) or from the natural content of rocks upon which lichens often grow (not a problem with usnea and other tree-based lichens).
Until more is known about potential adverse reactions to lichens, it is best to minimize ingestion of all of them, and especially to avoid prolonged ingestion of any products containing high levels of usnic acid.