DID THE HERBS CAUSE THAT?

essay by Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine, Portland, Oregon

One of my tasks at the Institute for Traditional Medicine (ITM) is to field questions from practitioners about their use of Chinese herb formulas. After more than 20 years of doing so, I've noted a distinct shift in the types of questions asked. Formerly, the questions were usually in reference to treating patients who presented a complex case or rare disease, where the practitioner wondered where to start with herbal therapies or they were unsure of how to progress from an initial treatment to a next stage of therapy. Recently, however, the questions are about the possibility that the herbs prescribed by the practitioner had been responsible for a negative reaction relayed by the patient, or whether the herbs could be prescribed at all, for fear of interactions with drugs the patient is already taking.

The reason for this shift, I suspect, is that there has been so much negative publicity about Chinese herbs, and about herbs in general. Patients and their medical doctors are very worried about the potential negative impact of taking herbs, and are often willing to very readily attribute dire consequences to their use. This problem is compounded by a lack of fundamental knowledge by many of the prescribing practitioners about what the herbs can and cannot do and what chemical constituents they contain.

I would like to relay two examples of incidents reported to me that help illustrate the nature of the situation. In the first instance, a patient was just a few days into a regimen of Chinese herbal therapies (taking tablets) when he experienced a sudden severe blurriness of vision that persisted. He went to his doctor, who noted that his pupils were markedly dilated, and subsequent visits to medical specialists were unable to determine what had happened. However, the pupil dilation in the absence of other obvious signs indicated to at least one of the specialists that the patient was suffering from a reaction to a chemical agent (it is well-known that some drugs cause pupil dilation). No sooner was he asked what he had recently taken than the Chinese herbs became the prime suspect. Lists of the ingredients (commonly used Chinese herbs reputed to be non-toxic) were examined, literature was consulted, and the tablets were sent off to a laboratory. Several tests of the patient were conducted, including a brain scan to check for a stroke, without finding any other cause.

The prescribing practitioner contacted me and asked if this response was an expected side effect of the herbs. I was also asked about possible mechanisms by which the herbs could cause this response, in terms of traditional Chinese thinking; e.g., did the tonic nature of the herbs (mainly yin and blood nourishing herbs with astringents) cause a worsening of internal wind that could have produced this response? From my knowledge of the herbs (including botanical sources and chemical constituents) and the theories of Chinese medicine (that the tonics involved would be interpreted as helping to calm internal wind, not worsening it), I assured the practitioner that the herbs were an unlikely causative agent. The practitioner then mentioned that between starting the herbs and experiencing the blurred vision, the patient (an elderly male with some typical problems associated with aging) had gone to a wedding party and consumed a lot of rich foods and alcohol. From the traditional Chinese medical perspective, that would be deemed a sufficient cause of the blurred vision (see: the ophthalmology text Essential Subtleties on the Silver Sea, translated by Evans and Unschuld).

A few days later, the nature of the situation was resolved. The patient's own eye doctor performed some more detailed tests and found out that his patient was suffering from macular degeneration and retinal tears. Checking the patient's prior records, the doctor found evidence from at least six months earlier that this problem existed in a milder form, but the diagnosis had been missed at that time. This disease can progress gradually, but may have sudden worsening. It is possible, though we cannot know for certain, that the excesses at the wedding party contributed to the sudden worsening. For the moment, the herbs are off the hook, but the practitioner involved still seems to believe that the administration of the herbs was a contributor, via an effect on internal wind.

A second case involved a woman in her twenties who had just started an herbal therapy. She was driving in her car, apparently had gotten dizzy and blacked out, and crashed. Thankfully, she was in slow traffic, so the crash did not cause any injury itself, but she was taken to the hospital. The attending doctors immediately deemed the Chinese herbs to be the cause of her black out. In this case, the practitioner and the patient were not readily convinced of the role of the herbs in this incident, but the practitioner experienced a second report of adverse reaction from the same formula at about the same time. Another patient complained that, after taking a single day's dose, she was agitated, was sweating excessively, and had insomnia. It would seem from these dual cases that the herbs caused a severe neurological response.

The herb formula was one that is very widely used, one of many preparations of Erchen Wan (Citrus and Pinellia Formula, a prescription for resolving phlegm). This particular batch had been used extensively without complaint, as has the formula in its numerous forms. A few days later, the practitioner reported that the problem with the herbs had been resolved. Upon further testing, the doctors discovered that the patient who blacked out not only had a form of epilepsy, but that she had a family history of epilepsy, and that this experience was likely the patient's first episode of a potential life-long disorder. The practitioner then relayed the fact that the other patient, who had complained of the nighttime agitation, was prone to such problems and had just gone through a very stressful time. The practitioner was sure that the herbs were not involved in the reported symptoms.

In the cases of blurred vision and blacking out, the symptom blamed on the herbs was rather severe, which led to further testing of the patients and eventual determination about causes, finally alleviating complaints about the herbs. I have been told of several other such alleged reactions that were either finally resolved or had a clear alternative explanation. However, in most cases, the purported herb reactions are less severe, and an alternative explanation is not developed due to lack of proper investigation. Therefore, the sense that the herbs are causing many adverse reactions can persist and grow over time.

It is important for practitioners to become more familiar with the nature of the herbs they prescribe and the expected responses to them, so as to be able to respond to concerns about and allegations of adverse reactions. One reason that practitioners may not know how to provide a satisfactory answer is that the normal and expected responses to herbs are not known: the practitioner doesn't have a frame of reference. The majority of herb texts do not cover this subject.

Generally speaking, about 95% of an herb (crude dried herb as appears in Chinese pharmacies) is medicinally inactive and comprised of carbohydrate materials such as cellulose, starch, and simple sugars; fats, such as heavy oils and simple fatty acids; and proteins, mostly complex structural proteins and enzymes with some free amino acids. In addition, there are vitamins, minerals, and other compounds that are typical of what is found ordinary foods. The presence of these ordinary substances, some of which are removed when making extracts, are the reason why the dosage of herbs needs to be so high compared to drug therapies.

About 5% of an herb, often less, is comprised of some active compounds that are either different from those found in foods, or similar to those found in foods but in larger quantities. These mainly fall into the following groups:

  1. Terpenes (subdivided into mono-, di-, tri-, and sesqui-terpenes); virtually all of these are safe compounds that promote circulation and calm agitation. As an example, the triterpenes of ginseng, zizyphus, bupleurum, and ganoderma can be consumed in quantities of several hundred milligrams to safely provide circulation-promoting and sedative effects.
  2. Flavonoids (subdivided into flavones, isoflavones, anthocyanidins, etc.); virtually all of these are safe compounds that promote circulation and alleviate allergy reactions. As an example, the flavonoids in ginkgo leaf, pueraria, and citrus are known to have these effects and are used in doses of several hundred milligrams.
  3. Pyrones, quinones, and other oxygenated compounds; virtually all of these are safe compounds that promote circulation and alleviate spasms and pain. As examples, the benzopyrones of tang-kuei, cnidium, and chiang-huo and the quinones of salvia are all used to aid circulation and relieve pain, and are used in doses of several hundred milligrams.
  4. Alkaloids; several alkaloids have the potential for significant adverse effects, because alkaloids often interact with the nervous system. However, Chinese herbs that rely on alkaloids are often selected because of their mild activity; most have antibacterial, fever reducing, and sedative effects. Examples are coptis, phellodendron, and sophora; even these herbs can have adverse effects if the dosage is too high and if the administration of high doses is continued over a long period. Nonetheless, the alkaloids of these herbs are often consumed in quantities of several hundred milligrams per day without adverse reactions.

A gram of herbal material that contains 5% of one of these groups of active constituents will provide 50 mg of those compounds. Thus, several grams of the herb can usually be taken while the amount of active components consumed remain within the hundreds of milligrams that are safe and without any significant adverse effects. Chinese herbs that have significantly toxic compounds, such as strychnos, datura, raw aconite, and croton, are not incorporated into the Western practice of traditional Chinese medicine.

In the cases of suspected adverse reactions, such as the cases I cited above, alkaloid components would be the primary suspect. But, the formulas involved did not include any significant amounts of alkaloids, making it extremely unlikely that the herbs could have played any role in the reported actions, especially with such short term use and with the modest doses consumed.

By knowing something about the content of the herbs, the types of activities to be expected from the active constituents, and the dosages involved, one can analyze most reports of potential adverse reactions and draw some tentative conclusions. Frequently, patients, medical personnel, and practitioners who have had limited training in herbal medicine will jump to conclusions about the role of herbs in producing a certain reaction. Information about the content of herbs, their pharmacology, clinical effects, potential adverse reactions, and other valuable data are available in English language books and journals, and from several organizations (including ITM and the Oriental Healing Arts Institute that have focused on these areas). It is important for practitioners to study such materials before patient complaints are received so that it is possible to provide a rational response promptly and initiate a proper investigation. A good understanding of the mechanisms and timing of various types of reactions (such as allergies and toxic responses), interactions (mainly between herbs and drugs), as well as the traditional Chinese interpretation of herb effects (such as contraindications), will make it possible to prescribe herbs with confidence and respond to concerns authoritatively.

Note: the above article appears in the Pacific Symposium News (2001).

APPENDIX: The Most Common Concern: Hypertension

The most frequent concern raised about the possible adverse effects of herbs is the impact on blood pressure. Blood pressure was not measured by traditional Chinese medical practitioners and is not detectable by pulse taking except in extreme cases of hypertension. Therefore, it represents a uniquely modern issue. In the U.S., hypertension is publicized as a silent killer and people are warned to have their blood pressure checked and to have high blood pressure treated promptly. Rates of hypertension among adults increase with age, and many people over age 60 have blood pressure in the range that is considered worthy of treatment or, at the least, careful monitoring on a regular basis.

Blood pressure can vary markedly from moment to moment. A small amount of exercise, even walking around, can raise blood pressure in many individuals. Emotional reactions can change blood pressure; a condition known as "white coat hypertension" is well known and refers to elevated blood pressure associated with anxieties about medical office visits; anger, anticipation, and hopelessness can also cause rises in blood pressure. Therefore, any individual blood pressure measurement can be an unreliable indicator of the person's general status and may reflect, instead, a momentary condition.

Many practitioners call ITM to ask if an herbal formula might be responsible for a blood pressure rise that a patient reported, or ask if it is alright to give a patient a certain formula, worrying about the fact that the patient currently has high blood pressure and not wanting the herbs to cause it to go higher.

None of the traditional indications for herbs are that they raise blood pressure, though there is one exception that, based on modern interpretation, involves raising blood pressure: high doses of ginseng (10-30 grams in decoction) are given for treatment of shock, a condition of sudden low blood pressure. By contrast, all reports from the Orient about the effect of normal doses of ginseng (1-3 grams powder each time, three times daily or 3-9 grams root in decoction in one dose or two divided doses) indicate that the herb lowers blood pressure or has no effect on blood pressure.

When pharmacology studies of Chinese herbs were initiated during the last half of the 20th Century, hypertension was a developing global concern, so herbs were studied for their potential to lower blood pressure. Dozens of Chinese herbs were immediately reported to have hypotensive effects, and the number of herbs with such action that have been reported in the literature is now over 100. For example, in the book Pharmacology and Applications of Chinese Materia Medica, published in 1986, 98 of these are listed. Contrary to opinions expressed by many Western practitioners of Chinese medicine, yang tonics are not known to raise blood pressure; instead, they tend to lower blood pressure. The best known of the yang tonics for lowering blood pressure is eucommia, an herb that has been featured in several Chinese patent remedies for hypertension (e.g., Fufang Duzhong Pian; Compound Cortex Eucommia Tablets, indicated for symptoms of hypertension). Other yang tonics that are reported to lower blood pressure include cistanche, cuscuta, epimedium, and morinda. In fact, a relatively new formulation (first published in 1975) for treating menopausal hypertension, Er Xian Tang (often called Two Immortals Decoction), relies on the hypotensive action of morinda and epimedium. The effectiveness of the formula has led to it being listed among famous traditional prescriptions by many authors.

It has been well publicized that the alkaloid ephedrine, the main active component of ma-huang, can raise blood pressure (see: Safety issues affecting Chinese herbs: the case of ma-huang). The effect was not noted in healthy young adults taking 20 mg at one time (an amount that is obtained in some decoctions, but not in Chinese herbal pills which often provide less than half that amount), but the effect can occur with high doses and in persons with pre-existing hypertension. Ma-huang is the only Chinese herb that contains any significant amount of ephedrine (there is a tiny amount in pinellia). A compound chemically related to ephedrine, called synephrine, is found in herbs derived from citrus (e.g., citrus, chih-shih, chih-ko, aurantium, etc.); this alkaloid may also cause hypertension if taken in high enough dosage (see: Synephrine: is chih-shih toxic? ). Other than these, herbs potentially causing hypertension have not been identified. There are no herbs that are specifically known to treat hypotension (the use of ginseng for shock is only for the emergency condition and not for chronic hypotension), though there are a variety of formulations that have been tried and may have limited success.

Despite the likelihood that Chinese herbs are suitable for use in persons with hypertension and that they do not cause hypertension, worries will persist. Negative publicity about ma-huang, repeated warnings about using ginseng in relation to hypertension (see: Safety issues affecting Chinese herbs: the case of ginseng), and other reports about apparent adverse reactions to Chinese herbs lead many to blame Chinese herbs for any case of unanticipated blood pressure increase. Practitioners should evaluate their patient's concerns, and their patient's current blood pressure and its variability, before prescribing Chinese herbs.

May 2001