THE NATURE OF GINSENG

From Traditional Use to Modern Research

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

The way in which ginseng is used depends on one's understanding of its indications, effects, and proper dosage. Unfortunately, the views expressed in today's popular literature about ginseng rarely reflect either the traditional use of the herb throughout Chinese history or the current consensus of scientific knowledge about ginseng and its active constituents. Further, research aimed at demonstrating the effectiveness of ginseng for several applications is of varying quality; the results can be misleading if study design and reporting are not critically analyzed before accepting the conclusions offered by the authors. This article reviews both the traditional use and evolving modern interpretations of ginseng. In particular, the dosage of ginseng to be consumed is considered because of substantial differences between Asian and Western recommendations.

GINSENG IN TRADITIONAL CHINESE LITERATURE

Ginseng was originally used as an herbal medicine in ancient China. There are written records about its properties dating back to about 100 A.D. Traditional Chinese medical literature is an important resource for understanding ginseng because virtually all proponents of ginseng refer to its long history of use as a reason to recommend it as a health product. Scientific investigations of ginseng are usually aimed at attempting to confirm the validity of the traditional uses. Thus, the historical basis for consuming ginseng is still relevant.

The basic framework of the traditional Chinese culture that is of such interest to the West coalesced around a group of ideas and practices that matured during the period 500 B.C. to about 200 B.C. Essential contributions included: development of a uniform writing system based on ideographic characters that are still recognized today; the philosophical systems derived from the trio of Confucianism, Taoism, and Buddhism; solidification of the organizing principles of Yin and Yang and the Five Elements; the medical system incorporating acupuncture and herbal formulas; and institution of the Imperial government system. Then, during the Han Dynasty (203 B.C. to 220 A.D.), these critical cultural developments were formalized and the details were recorded for posterity. Any investigation of the origin of a fundamental Chinese concept, such as the meaning and value of ginseng, begins with a study of this period; the beginnings of ginseng use and the description of its effects can be traced by examining the written records.

The oldest medical document of China, buried around 170 B.C., during the early Han Dynasty, was excavated from a tomb in 1973 at Mawangdui, the "mounds of the horse emperor," near Changsha, the capital of Hunan Province in central China. This record suggests that the traditional Chinese medical system was still forming at that time, and had not yet reached the relatively consistent set of theories and rules that emerged soon after. For example, the system of meridians, the channels of the human body that became a central component of the acupuncture system, was different at this time. A scroll listing herb formulas found at the burial site, which has been dubbed Wushier Bingfang (Prescriptions for 52 Diseases), reveals that the early Chinese herb formulas usually employed two to three ingredients, compared to the more complex formulas used later, typically containing from six to fifteen herbs. Apparently, ginseng is not included in these early formulas. (1)

The text that serves as the key source book for all of Chinese medicine, the one to which every physician refers for wise sayings of unquestionable authority, is the Huangdi Neijing (Yellow Emperor's Classic of Medicine, 2). Based on the writing style and references to various cultural matters, this book was probably written between 100 B.C. and 100 A.D. It describes the cause and development of diseases and specifies some acupuncture therapies for them. Herbs are barely mentioned, and only in a general way, without reference to specific herbs. Ginseng, despite its fame in years to come, is not mentioned.

The first book that serves as a compendium of herbal knowledge for the Chinese tradition is the Shennong Bencao Jing (Classic Herbal of Shennong) written around 100 A.D. Shennong was a mythological figure, the divine farmer, who was said to have tasted 70 different herbs each day, determining which ones were useful for humans. Of the thousands of herbs he tasted, 360 were deemed suitable: not too poisonous, but having a nature and taste that would impart medicinal effectiveness. These were recorded in this text, a translation of which is now available (3). This classic includes the first written record of ginseng as a medicinal agent. The use of ginseng in China, and, indeed, throughout Asia, is based largely on the description in this book, one that has been passed on from generation to generation since that time. The traditional Chinese medical system is highly conservative: rather than seeking out innovations, physicians and scholars constantly strive to stay true to the original. Thus, it is essential to know the classical understanding of ginseng to grasp its meaning in subsequent centuries.

TRADITIONAL CHINESE MEDICINE CONCEPTS

Each herb in the Shennong Bencao Jing is described by only a few sentences that, despite their brevity, convey much to the traditional physicians. In order to understand the section on ginseng, one must be familiar with the two basic descriptive categories for herbs in traditional Chinese medicine-nature and taste.

According to classical theory, the nature (Chinese: xing) of an herb depicts not only what the herb is like inherently, but also how it will interact with other herbs in a formula and the effect it will have on those who consume it. The herb's nature is classified either as cold, cool, neutral, warm, or hot. In general, warm or hot natured herbs can be used to treat disease conditions that are characterized as being cold (e.g., feeling chilled, aversion to cold environment, watery discharge, pain alleviated by warmth and pressure, desire for warm drinks). Herbs that are cool or cold in nature can be used to treat disease conditions that are characterized as being hot (e.g., feeling feverish, aversion to hot environment, thick discharge, pain alleviated by cold and worsened by touch, desire for cold drinks). Neutral herbs can be used for any disease condition. Because of their mild nature, both warm and cool herbs can be used with considerable flexibility and might be incorporated into treatments for either hot or cold type diseases; by contrast, the more extreme-natured herbs, classified as hot or cold, have to be used with some caution.

The taste (wei) of an herb represents how the herb was formed from the basic elements of the universe, what therapeutic properties it has, and what organs it will affect. There are five basic tastes: sweet, acrid (also called pungent or spicy), bitter, sour, and salty. An herb can be described as bland (rather tasteless), which represents an added sixth category. The ancient Chinese concept of the internal anatomy involved five fundamental viscera: spleen, lung, heart, liver, and kidney-each one associated with, and particularly influenced by, one of the five tastes. The connections that were made in ancient times between the tastes and organs can be explained by simple observations; for example, the kidney yields the salty tasting urine and is therefore associated with the salty taste. As an example of the relationship between taste and effects, sweet (pleasant tasting) herbs and foods are said to enhance the function of the "spleen" (which refers not to the anatomical spleen but to an organ system that mainly comprises the digestive functions) and to nourish the body.

The Shennong Bencao Jing says this about ginseng (3):

Ginseng [renshen] is sweet and a little cold. It mainly supplements the five viscera. It quiets the essence spirit, settles the ethereal and corporeal souls, checks fright palpitations, eliminates evil qi, brightens the eyes, opens the heart, and sharpens the wits. Protracted taking may make the body light and prolong life. Its other name is renxian. Yet another name is guigai. It grows in mountains and valleys.

To appreciate fully the ancient description of ginseng, here is an elaboration of the statements made (for information about the name of the herb, see the article: The meaning of shen in renshen):

• Ginseng is sweet: Anyone who tastes a ginseng root today will find it quite bitter. The freshly picked root is sweeter (has a somewhat pleasant taste compared to many other herbs), but, more importantly, the designation of the root as sweet is partly based on the idea that sweet is the underlying inherent taste within the herb that reflects its actions. Like other sweet herbs, it is believed that ginseng will supplement the spleen, calm irritation, and nourish the body. Later Chinese texts often mention the bitter taste as well.
• a little cold: The action of the herb is relatively mild, in contrast to a cold herb, but its nature is still like that of a cold herb, able to alleviate heat syndromes. The combination of sweet and cold together has the effect of calming nervous agitation: the sweetness alleviates irritation and the coldness calms the internal fire that agitates the human spirit.
• supplements the five viscera: Ginseng does something more than most of the sweet herbs; it not only benefits the spleen, but also the other four systems of the body: liver, kidney, heart, and lung. One implication is that ginseng greatly improves the ability of the spleen to draw nutrients out of food and distribute them to the other organs. It serves as a nutritive aid, but does not provide nutrients.
• quiets the essence spirit: The essence spirit can be broadly interpreted as referring to the mind. Thus, ginseng quiets the mind. By taking ginseng, excessive mental chattering calms down.
• settles the ethereal and corporeal souls: The ethereal soul (hun) and corporeal soul (po) refer to fundamental forces within the body. The ethereal soul is believed to reside in the liver and to be responsible for dreams; the unsettled hun causes one to have disturbing dreams, even nightmares. The corporeal soul is said to reside in the lungs, and to be responsible for maintaining the integrity of the physical body. Persons who develop life-long degenerative diseases are said to suffer from scattering of the corporeal soul, often the result of being frightened. It could be said that ginseng calms the distressed mind while strengthening the body.
• checks fright palpitations: When a person is frightened, he/she experiences an irregular heart beat and palpitations. Anxiety attacks and panic attacks correspond roughly to fright palpitations. Ginseng helps calm the heart (the resting-place of the spirit) so that it does not overly react to external stimuli nor to internal mental worries: equanimity is restored.
• eliminates evil qi: Evil qi refers to influences from the environment that cause diseases. Herbs that nourish the viscera, like ginseng, are usually not attributed the ability to expel the evil that is causing disease; more often, such herbs are said to protect the body from evil qi (evil can't get into the strong and well-nourished body to cause disease) or to help the body recover its strength once the evil has been eliminated. Ginseng can be taken when a disease is present to help cure it by eliminating the evil qi. Some later authorities disagreed with this view, suggesting that ginseng had only tonic properties and should not be taken while evil qi was still present for fear of enticing the evil to stay within the body.
• brightens the eyes, opens the heart, and sharpens the wits: The eyes are the windows to the mind; the heart is the residence of the mind, and the wits are the expression of the mind. This section says that by taking ginseng one's mind will not become dull. If the heart becomes closed, if the mind becomes overwhelmed with thoughts, if the spirit is clouded and the eyes therefore dim, then a person's fundamental nature will be prevented from attaining its ultimate expression: the person will be timid, unhappy, even depressed. When the heart opens and the mind quiets, the true nature will be expressed and the person will display sure purpose, will, and courage, able to accomplish great things.
• protracted taking may make the body light and prolong life. This phrase is included in reference to the intensive efforts undertaken by Taoists pursuing immortality during the Han Dynasty period. They believed that one could shed the physical body and float into the heavens as an immortal being. Most of this transformative (alchemical) process was accomplished with minerals, such as cinnabar (mercury sulfide), which slowly poisoned the Taoists' bodies due to prolonged exposure. One consequence was that they lost weight: at the time, their shrinking flesh was taken not as an indication of poisoning, but as a sign that they were shedding their earthly body to leave only the heavenly body. This section does not indicate that ginseng can be used as a weight loss herb for the obese, nor does it even suggest that one can live longer on this earth by taking the herb regularly; it refers specifically to the Taoist concept of transformation to an ethereal immortal.

The Shennong Bencao Jing does not record anything about how to use ginseng (e.g., dosage, preparation, duration of use), but only presents its nature, taste, and effects.

MEDICINAL USE OF GINSENG IN ANCIENT CHINESE MEDICINE

The first book that describes with some details the actual medical applications of herbs is the Shanghan Lun (Treatise on Treatment of Diseases Induced by Cold). Shanghan is the name of a disease category depicted in the Yellow Emperor's Classic, involving a serious illness initiated by cold evils and progressing, sometimes rapidly, from the exterior of the body (skin and muscles) to the interior (viscera). This text, written at the end of the Han Dynasty, is still studied carefully today by all who practice traditional Chinese medicine. Chinese medical scholars have cautioned physicians repeatedly to study and pay attention to the formulas mentioned in this text, and to avoid straying too far from the principles described therein. There are at least three English translations currently available, of which the one by Hsu and Peacher (4) is recommended because of their attempts to stay true to the original by using an old version of the text for translation: a reprint of one first published in 1060, during the Song Dynasty (960-1279). At that time, the Shanghan Lun was divided into two books, the first carrying the original title and the second given a separate title: Jingui Yaolue, or Prescriptions of the Golden Cabinet, which Hsu has also translated (5).

The Shanghan Lun presents 107 formulas that had been collected by the physician Zhang Zhongjing. Ginseng is an ingredient in 21 of the formulas, clearly being an important herb. One of the representative formulas containing ginseng is called Lizhong Wan, or the Pill to Rectify the Center. Here, "the center" refers to the spleen system, and what is being rectified is its disturbance, marked by upper abdominal discomfort and digestive system disorders such as loss of appetite, nausea, burping, vomiting, or diarrhea. As indicated above, the "spleen" in traditional Chinese medicine refers, in part, to the digestive tract, not the specific anatomical organ called the spleen in Western medicine. In this text, the cause of the disease is thought to be excessive cold (a type of evil qi) in the environment. After entering the body, if the evil qi has not been dispelled, it penetrates to the interior and damages the function of the spleen. The formula is said to drive out this debilitating cold influence.

The formula contains equal parts of four herbs: ginseng, ginger, licorice, and atractylodes. The first three herbs are familiar to most people with even a small knowledge of Chinese herbs; atractylodes is commonly used in China for treating digestive system disorders. The herbs are prepared as a pill (wan). The intended effect of taking the formula is to feel warmth in the abdomen: this effect comes mainly from the ginger. If that warmth is not felt, one can increase the dosage from 1-2 pills to 3-4 pills. Alternatively, the herbs can be decocted (put in water that is then boiled). The entire batch of tea is taken in one day.

The question of how much ginseng to take in order to gain its purported beneficial effects is one that is important to the modern situation where recommendations vary widely. Estimates of ginseng dosage in its traditional applications can be derived from the ancient texts, such as the Shanghan Lun. The instructions for preparing Lizhong Wan are as follows: grind the herbs to powder; mix them with honey; and then form pills the size of an egg yolk. Such pills are quite large, typically weighing about 9 grams, of which about 6 grams comes from the herbs and 3 grams from honey. They cannot be swallowed whole, but are either chewed up or added to hot water, dissolved, and consumed as a tea. This same type of pill is produced today by the millions at Chinese patent medicine factories, such as Beijing's Tong Ren Tang, founded in 1669 (during the Qing Dynasty), one of the largest of the hundreds of such factories in modern China. The pill, as described above, has about 1.5 grams of ginseng and the daily dose ranges from 1-4 pills, or 1.5-6.0 grams of ginseng. For other ginseng-containing formulas in the Shanghan Lun that are made in decoction rather than pill form, the ginseng dosage is about 1.3-3.9 grams. Thus, the range of daily ginseng doses recommended was from as little as 1.3 grams for a single dose, to as much as 6.0 grams for a double dose (as might be needed in some cases).

The ginseng in use at this time (end of the Han Dynasty), and for centuries afterward (to the end of the Ming Dynasty, 1644), was all wild ginseng. Ginseng hunters would search through the forests of northeastern China to find the plants, carefully remove them from the soil, dry them, and bring them to the herbalists who, for the most part, were working further south. Modern proponents of ginseng have argued that wild ginseng is much more potent than the cultivated type. If this is the case (and it has not been confirmed), then the dosage of cultivated ginseng to be used today, in a similar application to the ancient uses, might be even higher than that described above for the wild-harvested roots.

Unfortunately, wild ginseng plants do not flourish under pressure of collection because of limited seed germination and slow maturation. As a result, the supplies of ginseng in China gradually receded to the regions that were increasingly inaccessible in the far northeastern mountains. The ability of herbalists to obtain ginseng declined, and the cost increased, making it available only to those who were wealthy. Despite its increasing rarity, ginseng was still mentioned in the Chinese medical literature and included in formulas to treat various ailments, especially those of the digestive system. Perhaps one of the most famous of all the ginseng-containing formulas (at least, of those in which ginseng is a primary ingredient) was recorded in an Imperial herb formula guide of the Song Dynasty (960-1279). The formula, called Si Junzi Tang, or the Four Gentleman Decoction (see: What's in a name? The four gentlemen decoction), was recorded in the Taiping Huimin Hejiju Fang (Formulary of the People's Benevolent Pharmacy of the Taiping Era, 1110). This text described formulas made at the Imperial pharmacy. It is the source of many of the formulas used today, especially the traditional formulas manufactured in Chinese patent medicine factories as pills.

Si Junzi Tang is almost the same as Lizhong Wan. There is substitution of one herb: ginger is deleted and replaced by the fungus called fuling (common name: hoelen or poria). Unlike Lizhong Wan, which is intended to warm up the abdomen with the spicy warming herb ginger, Si Junzi Tang is supposed to help assure that the water ingested, both as beverage and as the moist part of food, is extracted and circulated (failure to do so leads to loose stool or diarrhea). Hoelen is a bland tasting and neutral herb that is reputed to soak up and redistribute moisture.

This formula is reported in every modern text on traditional Chinese herbal formulas; it is usually the first one listed in the section devoted to qi tonic formulas. A typical dosage pattern for Si Junzi Tang is (6):

The dosage of ginseng in this formula, as well as the dosage of the other ingredients, is consistent with the amounts used in modern Chinese practice. In some other Chinese texts, as summarized in Chinese Herbal Medicine Formulas and Strategies (7), the dosage of the herbs for this particular formula is somewhat lower, with ginseng administered at 3-9 grams.

There are two other famous prescriptions with ginseng that deserve special mention. These were also formulated during the Song Dynasty: Buzhong Yiqi Tang (Decoction for Tonifying the Center and Regulating the Qi, from a book published in 1249) and Guipi Tang (Decoction for Restoring the Spleen; from a book published in 1253). Both prescriptions are used to aid the digestive functions. The former is usually selected for those who have been debilitated by prolonged illness, especially when the illness has come about from poor habits: eating irregularly, working too hard without enough rest, and anxiously worrying. The latter is mainly used for those who suffer from mental agitation, anxiety, and insomnia as a syndrome secondary to deficiency of the spleen (guipi = restore the spleen). When prepared as a decoction, the ginseng dosage in the former is 9-12 grams and, in the latter, 3-6 grams (7).

In sum, ginseng was historically given mainly for syndromes that involved digestive system weakness and the dosage of ginseng ranged from about 3-9 grams in most instances, with low dose administration of about 1.3 grams per time and high dose administration of up to 12 grams per day. The modern Chinese Materia Medicas are in agreement with these amounts of ginseng, namely a recommended daily dose of 3-9 grams for a one day dose for standard applications (16, 30).

The duration of using ginseng, alone or in formulas, was not specified in the early texts. In some instances, it was understood that only one or two doses would be enough to change the course of a disease and help the patient onto the path to recovery. In other situations, it was understood that ginseng would be taken for many days to change a persistent pattern of imbalance. Due to the rarity and high cost of ginseng, it was usually used only so long as deemed necessary. The Taoists-some of whom took ginseng daily in an attempt to become an immortal-collected their own herbs to pursue their goals, spending much of their time wandering the mountains in search of ginseng and other important tonics.

UPDATING THE CONCEPT OF GINSENG

The first known treatise devoted specifically to ginseng was written during the 16th century (Ming Dynasty). Excerpts of it appeared in a book that remained essential to Chinese herbalism for the next four centuries and even today: Bencao Gangmu (Great Compendium of Herbs). The author of Bencao Gangmu, Li Shizhen, is revered to this day for his efforts to organize herbal knowledge and sort through the morass of misinformation (see: Li Shizhen: Scholar worthy of emulation). The ginseng treatise had been written by his father, Li Yenwen, and this part was published in the Bencao Gangmu, which was published in 1596. (24):

Used fresh, ginseng displays a cool nature. When it is used after preparation [steamed, red ginseng], its nature is warm. The slight sweet taste strengthens the yang; the somewhat bitter taste strengthens the yin. Nature [xing] controls the genesis of things: their origin is in heaven; tastes control the completion of things; their origin is in the earth. Nature and taste, genesis and completion are realizations of yin and yang. The cool nature of fresh ginseng expresses the yang influence of spring, namely, of genesis and development. This is the yang of heaven. It has the nature of rising. Sweet is a taste that has been formed through transformation of moisture and earth. These are the yang influences of earth. They have the nature of floating. The somewhat bitter taste has been formed through reciprocal interaction of fire and earth. These are the yin influences of earth. They have the nature of descending in the body.

Taste and nature are both equally weak in ginseng. Whatever has a weak nature descends in the body when fresh, and rises when prepared. Whatever has a weak taste rises in the body when fresh and descends when prepared. In case of illness in which the earth [spleen] shows a depletion and the fire [heart] shows vigor, the weak cool nature of fresh ginseng is suited to diminish the blazing of the fire and to replenish the earth. This could be called a pure use of ginseng's nature.

In the case of illness characterized by depletion in the earth and weakness in the lung, the sweet taste and warm nature of prepared ginseng is suited to replenish the earth and to generate the metal [associated with lung]. This could be called a pure use of ginseng's taste....

One can take from this description that ginseng, whether "fresh" (indicating that it is not processed; i.e., dried, white ginseng that is cool in nature) or prepared (i.e., steamed ginseng, which turns red in color and is warm in nature), has a mild quality and effect: both its nature and taste are weak. The author is illustrating that ginseng can both float and sink in the body (its taste working in one direction and its nature in the other), meaning that it can be used in treating ailments affecting both the upper and lower body.

Today, some Western herbalists depict ginseng differently: as being strongly stimulating and overly heating, a view that is quite contrary to the traditional one, even for the processed (red) ginseng, described by traditional doctors as being only warm in nature. In fact, much of the red ginseng from China, such as Jilin (Kirin) ginseng, is described in China as having a nature that is neutral, reflecting its mildness.

Dr. Shiu-ying Hu translated 42 recipes with ginseng from Li Shizhen's compendium (60). They are used for conditions such as having poor digestion, "stomach trouble," nausea, or vomiting; being thirsty all the time; feverish diseases with excessive sweating, cough, or laryngitis; bleeding disorders, including internal hemorrhage, nose bleeding, blood in the urine, and post-partum bleeding; and pregnancy disorders. Most of these disorders can be categorized as stomach and spleen problems and heat syndromes. Typical daily doses for these Ming Dynasty formulas are 8-15 grams of ginseng in decoction or 6 grams in powder form, made into pills.

GINSENG MISUSE AND GINSENG SUBSTITUTES

Declining wild resources of ginseng eventually led to considerable distortions in concepts about the nature of ginseng and how it could be used. Ginseng sellers exaggerated the benefits of the herb to justify the increasing price. During the Qing Dynasty (1644-1911), ginseng was known as the herb that could restore the dying to health and restore the dead to life. Wealthy families would squander their life savings on ginseng roots to save a dying family member. When ginseng failed to accomplish its claimed revival and the person died, ginseng was sometimes blamed for the death. Hence, ginseng gained a reputation as a highly dangerous herb: one that could save lives or snuff them out. All depended on using it correctly, so it was said that a misdiagnosis and inappropriate prescription for these terminally ill patients would be quickly fatal. The underlying concept, including both the versatility of ginseng and an allusion to dire consequences, was described by Xu Dachun (8) in his brief essay on ginseng (1757, during the Qing Dynasty):

Since ginseng is a substance rich in influences [qi] and full of vigor, it is able to supplement depletion and stop the loss of proper influences, no matter whether a patient's illness is related to wind, cold, summer-heat, dampness, phlegm, fire, or some binding of influences within the body. An application of ginseng is always appropriate when the evil influences that caused a patient's illness have left the body, but the proper influences are still weak; or when only a little of the evil influences remain, but the proper influences are exhausted; or when evil influences have penetrated deeply into the body and proper influences are themselves too weak to drive off the evil influences.

In order to support the elimination of evil influences by means of herbs, one must give the patient ginseng together with other herbs that are capable of driving off the evil influences. However, before one applies ginseng, one should examine whether the disorder to be treated is minor or serious [take into account the balance between the proper and evil influences], and only if this is taken into account will the effect of rescue from danger or of strengthening that which is already bent [damaged] appear as a matter of course. If one fails to investigate, though, whether evil influences are present or not, and whether the person suffers from depletion or repletion, and if one administers only warm or hot substances of a purely supplementing nature [as is common practice today due to current medical theories], then one will merely supplement the evil influences and help them settle down. In minor cases, the evil influences will, as a result of such mistaken therapy, never leave the body again. In serious cases, death is inevitable.

In other words, if the pathogenic influence has not been removed or at least tamed, one must combine ginseng with other herbs that have the effect of dispelling the evil, but not with other herbs that have a tonifying nature; otherwise, the disease can become permanent or even cause death. A common saying at that time was translated as: "Nourishing the body with tonics when a pathogen is present is like inviting a robber into a comfortable home; he would gladly enter and not leave, taking time to steal all its valuables." As a result of the new view of ginseng as a remedy to rescue those close to death with a potential for harm if misprescribed, Zhang Lu, a physician of the Qing Dynasty, commented: "Some people look upon ginseng as poison or a sword [two-edged, able to provide help, but also to destroy], and stubbornly refuse to use it." (9)

An example of this mixed thinking about ginseng was relayed by physician Cheng Maoxian at the beginning of the Qing Dynasty period. He described in detail the treatment of a very difficult case, a 63-year-old woman suffering from a disease that came on suddenly and led to virtual inability to swallow; everyone was sure that she would soon die. Cheng explained his next therapeutic steps (45):

Her chest still was not free, so next I used Shen Ling Bai Zhu San [Ginseng and Atractylodes Combination]. The lady knew that I was using ginseng and feared that her chest would not ease but be stopped up from excessive supporting action. For this reason, over several days I added one and one-half qian [4.5 grams] of ginseng without letting her know. After these doses, her chest was opened and her stagnation downward abated. One day, the lady said to her son Shunian, "In the last few days, my gullet has felt open; don't use ginseng any more." Shunian murmured his assent but together with my unworthy self, he secretly added ginseng without ill effects for several days. ... Though the disorder was grave, she was restored to life. Half the merit was Shunian's, for the two reasons that he was a filial and friendly gentleman. First, he did not spare the ginseng; and second, he gave me complete charge. Had he looked for overnight success, or feared to use ginseng and huangqi [astragalus root (Astragalus mongholicus Bunge, Fabaceae); another tonic herb with action similar to ginseng], or, taking alarm, had changed doctors, the lady his mother could scarcely have preserved her life.

Ginseng and Atractylodes Combination is an expanded version of Si Junzi Tang, described previously. This story relays quite well the frustration that some doctors felt in the growing myths about the dangers of ginseng.

It was during this time period that ginseng gained a reputation for being excessively supplementing, and, by virtue of being linked with other supplementing herbs that were classified as warming, it also gained a reputation by some as a warming herb. An herbal published in 1757 (52) described ginseng as warm in nature and included the comment that "the effects of ginseng are superior to all other drugs." An explanation of Cheng Maoxian's application of ginseng in the above case is provided by the description of ginseng in this herbal: "It has a great ability to supplement the original qi in the lung. It drains internal fire and eliminates heat causing, in the chest, a feeling of uneasiness. It generates body fluids and quenches the thirst." Here, it is attributed a cooling property: draining fire and eliminating heat.

Stories about the rarity of ginseng during the 19th century were relayed by Western visitors, and several of their commentaries are told by Pamela Dixon in her book Ginseng (53). The Dao Guan Emperor (1821-1851) recognized that ginseng was on the verge of extinction and issued an Imperial decree that forbade its collection. A report in the Peking Gazette of 1884 stated that 20 ginseng roots-a large quantity at that time-were sent to the Guan Xu Emperor (the last Chinese Emperor to serve a full life in office).

The primary response to the rapidly diminishing supplies of ginseng was for herb collectors to flood the market with substitutes. The main one selected as a match for ginseng was codonopsis (Codonopsis pilosula), an herb botanically unrelated to ginseng which, nonetheless, was said to be about the same in effects, only safer, cheaper, and abundant. Although the root just barely resembles the ginseng root, by this time in China's history virtually no one knew what ginseng looked like, so merchants could call it "ginseng." The Chinese name for the herb, dangshen, indicated that it was ginseng from the Shandang region (shen is the key term to describe ginseng or a ginseng-like herb); Shandang had been the principal source for the preferred quality Panax ginseng, a plant hunted to extinction in that area centuries ago.

Codonopsis hadn't appeared in any of the herbals prior to the Qing Dynasty, but had received brief mention in the Bencao Gangmu. Some doctors of the Qing Dynasty regarded dangshen as the correct ginseng to use, being superior to renshen (ginseng) for most applications (22). Codonopsis became an official substitute for ginseng, widely used as such today, but the Chinese market has had numerous other substitutes as well. Table 1 lists herbs that are used as substitutes for ginseng, according to recent texts (25, 29).

Table 1: Herbs Used as Substitutes for Ginseng in Traditional Chinese Medicine.

Several of the ginseng substitutes have a confirmed close relationship with ginseng in terms of flowering plant evolution (34). They may contain similarly structured active components and/or present an appearance that is reminiscent of ginseng. A few of them are potentially toxic (e.g., the plants of the families Solanaceae and Phytolaccaceae), though their preparation in Chinese formulas has not been associated with any toxicity problems evident to Chinese herbalists. It is possible that some of the complaints about the dangers of ginseng raised during the Qing Dynasty arose from incidents where certain ginseng substitutes were improperly used. An illustration of this problem was presented in humorous light in the 1994 Jackie Chan film Drunken Master 2: a highly valuable ginseng root becomes lost, and is hastily replaced by the root of a garden plant that nearly causes death of the patient who doesn't know what a real ginseng root looks like.

The broad range of substitution options for ginseng helps illustrate the fact that the actions of Panax ginseng were not seen as unique. Rather, the therapeutic effects could be attained, to some extent, from other plants. In a few cases, the active constituents of the substitute herbs are similar. For example, modern investigations reveal that the saponin components of platycodon have a structure very similar to that of the ginsenosides. By such analysis of active constituents, it was found that a plant that had only been used as a folk remedy in China, jiaogulan (Gynostemma pentaphylla), contains some of the same saponins as those found in ginseng, and recently has been adopted as an inexpensive ginseng substitute. Another modern ginseng substitute is Eleutherococcus senticosus, known as eleuthero ginseng or Siberian ginseng. Its original Chinese name, ciwujia (spiny wujia) has been updated to reflect its use as a ginseng substitute: wujiashen (ginseng-like wujia). Today, virtually all Chinese medical texts and journal articles-reflecting actual practice in Chinese clinics-describe herbal formulas with codonopsis where ginseng would formerly have been indicated as the appropriate herb. Codonopsis contains none of the active components of ginseng.

WESTERN VIEW OF GINSENG

Among the first Westerners to attempt to penetrate the veil of Chinese herbal medicine were the British physicians F. Porter Smith and G.A. Stuart, working in China at the end of the 19th century and into the early 20th century, as the Qing Dynasty came to an end. They wrote (10):

Ginseng, with the Chinese, is the medicine par excellence, the dernier resort [last recourse] when all other drugs fail; reserved for the use of the Emperor and his household, and conferred by Imperial favor upon high and useful officials whenever they have a serious breakdown that does not yield to ordinary treatment, and which threatens to put a period to their lives and usefulness.... The ordinary ginseng of the markets has been studied and has not been found to possess any important medicinal properties. But the Chinese describe cases in which the sick have been practically in articulo mortis, when upon the administration of ginseng they were sufficiently restored to transact final items of business.... It is prescribed in nearly every kind of disease of a severe character, with few exceptions, but with many reservations as to the stage of the disease in which it may be administered with the greatest benefit and safety. Much of the ginseng on the market consists of Campanulaceous roots [i.e., codonopsis, adenophora, platycodon], substituted for those of the Araliaceous Panax. The former roots, while in a general way resembling those of the true ginseng, are more or less hard and woody, and free from worms, while the latter is succulent and very liable to attack by insects.

The main use of ginseng, depicted here, was for those who were severely ill, not just those who suffered from digestive system disturbance. The ginseng used by the Emperors and their households was the wild Manchurian ginseng; the market ginseng consisted mainly of cultivated roots (as used today) and substitute roots of codonopsis or other herbs. All the market samples were declared to be virtually worthless from a medicinal point of view, an opinion held by some researchers and physicians today with regard to ginseng itself.

The statement by Smith and Stuart-about failing to find any important medicinal qualities in ginseng-refers to the initial investigations by the scientific method of this highly acclaimed herb. Ginseng seemed to hold great promise, based on the extravagant Chinese claims, yet little turned up when it was studied. Often, the effects reported by one researcher contradicted those of the next, and a variety of explanations were devised to explain the results. As described in the book Korean Ginseng (21): "Every investigator had his own opinion about the action of ginseng." Even later, this concern lingered. In a report at the 1978 Ginseng Symposium in Korea, Prof. E.J. Staba of the University of Minnesota College of Pharmacy said, "The pharmacological effects reported for ginseng and its extracts are varied and controversial (55)." While some people simply dismissed the ginseng claims as the result of myths and superstitions, others decided to track down a basis for the reverence for ginseng.

IDENTIFICATION OF CHEMICAL CONSTITUENTS AND THEIR AMOUNTS

As a first step in separating the claims about ginseng from what it could actually do (from the modern scientific perspective) its active ingredients were sought. A history of these efforts was reviewed by Joseph Hou in an article (39) and with an overview in his book: Ginseng: The Myth and the Truth (22).

Ginseng was found to contain none of the potent alkaloids characteristic of many plants that were being relied upon to generate new drugs. Instead, the root is comprised mainly of carbohydrates: starches, cellulose, and free sugars (the sucrose content in fresh ginseng is about 25%, explaining the sweet taste, and the total sugar and starch content is over 60%), the sort of things found in a carrot root (21). In fact, like carrots, ginseng can be used fresh as a health food or vegetable (46). Panaxynol, one of the acetylenic compounds found in ginseng, is identical to carotatoxin isolated from carrots (49).

A small amount, less than 5% of the tap roots, of a saponin (sugar bound to a triterpene molecule) was discovered in the ginseng roots. This component was shown to have some pharmacological activity. Saponins and their related triterpenes (e.g., oleanolic acid, a common component of plant oils) are found in numerous herbs and also in some food plants (e.g., soybeans, alfalfa sprouts, olives, and pumpkins).

For several decades, efforts have been made to carefully isolate and identify each of the ginseng saponins, which are the main bitter components of ginseng. These saponins, formerly called panaxosides, are now called ginsenosides; there are several variants, labeled R_a, R_b, R_c and so on, and then subsets of each labeled 1, 2, 3. As of 1999, it was reported that 34 ginsenosides have been identified in Panax ginseng roots (47); the dominant saponins in these roots are of the R_b series and are of the dammarane type. Most of the other saponins are present in miniscule amounts (the next largest group, the R_g series, also of the dammarane group, are present at about one-third the quantity of the R_b series in Panax ginseng; 64).

The ginsenosides are concentrated primarily in the root's cortical tissues (outer layers) compared to the quantities found in the interior portions. According to one Chinese report, the ginsenoside content of the root hairs (fibrous lateral roots which are mainly cortical type material) was 9.7%, while that in the thicker lateral roots was 6.4%, and that in the main tap root (which is the portion usually traded on the market, having little cortical material) was only 3.3% (17). An earlier European report gave the figures as 5-7%, 2-4%, and 0.7-1.7% for these ginseng root parts, respectively (35).

European evaluations of ginsenosides in ginseng samples frequently generate lower figures for ginsenoside levels than Asian studies. According to Chinese studies, the range of values for total ginsenosides for Panax ginseng roots (taproots) is 2.2-5.5%, with 4% being a typical amount mentioned in the literature (11, 15). European literature mentions 1.5% and 2.0% ginsenosides as a minimum level to be expected for the roots (Swiss and French Pharmacopoeias, respectively), with some studies revealing a range of levels from 0.7-3.0% (59). It is unclear whether the divergence in reported levels of ginsenosides between Asian investigators and European investigators is due to different selections of root material for testing, different handling of the roots prior to testing, or different testing methodology and interpretation. One possibility is that Asian researchers include a broader range of ginsenoside compounds, including some bound forms such as malonyl-ginsenosides, in their tallies. A discussion of this significant variability in reporting does not appear in the published reviews of ginseng.

Higher levels of ginsenosides than found in Panax ginseng (with a differing mix of individual subtypes) are reported for American ginseng (Panax quinquefolius), at 6.2-7.4%, and for Tienchi ginseng (san qi) of southern China (Panax pseudoginseng), at 3-8% ginsenosides, with some reported levels of 12%. In a study of ginsenosides in ginseng roots found on the Taiwanese market (40), it was reported that the highest content of ginsenosides was found in Panax pseudoginseng, followed, in order, by P. quinquefolius, P. ginseng root hair, and then red and white P. ginseng roots (tap roots, as commonly sold in stores).

Studies of ginseng processing, in which the roots are steamed soon after collection, indicate that red ginseng (often referred to in the literature as Radix Ginseng Rubra) usually has a higher ginsenoside content than white ginseng. During the process to make red ginseng, malonyl-ginsenosides are coverted to their corresponding ginsenosides by hydrolysis. According to a report on American ginseng, the steaming process used to produce red American ginseng increases the level of its ginsenoside Rb1 by as much as 100% through conversion of malonyl-R_b1 to R_b1. The acidic malonyl compounds are poorly absorbed in humans, but intestinal bacteria metabolize malonyl ginsenosides to neutral ginsenosides, which are better absorbed (44). A small amount of acetyl-ginsenosides are also generated from the malonyl-ginsenosides when preparing red ginseng (49). It has been proposed that some of the changes in ginsenosides that occur when white ginseng is steamed to produce red ginseng also arise during preparation of ginseng tea and ginseng extracts (57). Another factor influencing the difference in ginsenoside content between white and red ginseng is the removal or retention of the outer root skin. White ginseng is frequently prepared by peeling the root. Since the ginsenoside content is particularly rich in the peel, this processing results in a relatively low ginsenoside content. Red ginseng, on the other hand, is processed by steaming the unpeeled roots.

Although ginsenosides have been the focus of research on ginseng active constituents, other compounds in the root have been discovered to have biological activity. These include acetylenic compounds, peptide glycans, polysaccharides, pyran derivatives, and flavones (17). One can demonstrate pharmacological activity of these substances when they are isolated and concentrated; for example, the acetylenic panaxynol, panaxydol, and panaxytriol show cytotoxic activity in vitro. Such action is potentially of value in cancer treatments, but only if the cytotoxicity is highly specific for cancer cells. Similarly, the polysaccharides of ginseng, like those of the medicinal mushrooms, can enhance certain immune functions, as demonstrated in laboratory animal investigations (48). The dose of immunologically active polysaccharides when isolated and used clinically are about 1-3 grams (33). The amounts of these various non-saponin substances that are present in ginseng roots are very small: they are unlikely to significantly contribute to any of the purported clinical effects of ginseng when the roots or their extracts are consumed in ordinarily recommended quantities. Similarly, ginseng contains B vitamins (B1 and B2) and trace elements (mainly manganese), which have a therapeutic action in large doses, but the amounts consumed when taking ginseng are trivial compared to dietary sources.

PHARMACOLOGY EXPERIMENTS

With proper design, pharmacology experiments can help elucidate the physiological mechanism by which the herb produces certain observed effects. Tests can be conducted on whole herb materials (e.g., by adding the powder to the diet), herb extracts, isolated active fractions (i.e., groups of chemicals), or individual chemicals from the herb.

Several of the initial pharmacology studies of ginseng were based on a well-known story in China about the way to determine whether a ginseng root was genuine (22). "In order to test for the true ginseng, two persons would walk together, one with a piece of ginseng root in his mouth and the other with his mouth empty. If at the end of 3-5 li [3 li is about one mile], the one with ginseng in his mouth does not feel himself tired, while the other is out of breath, the ginseng is genuine." In several of the early pharmacology experiments (during the 1960s) ginseng was given to test animals (mice and rats) that were then forced to keep moving until they became so fatigued that they had to stop (usually a forced swimming test or forced climbing test). The ones given ginseng were reported to be able to carry on longer (22).

The effect of ginseng on preventing fatigue due to overworking was viewed as an "antistress" action, and other studies focused on ginseng's ability to protect animals from various other types of stress, such as heat and cold, low oxygen, exposure to ionizing radiation, and infections. These efforts were the source of the concept of ginseng, and other herbs, as adaptogens: substances with a relatively high degree of safety that helped the organism adapt to various types of stress.

Ginseng research was influenced also by the growing concern about cardiovascular diseases that had become the leading cause of death in developed nations. Since it was said in the ancient texts that taking ginseng regularly could prolong life, it seemed reasonable to demonstrate that ginseng could reduce the risk of death from cardiovascular disease. To give credence to this outcome would require massive clinical trials with people taking either ginseng or a placebo over a period of many years, but, to start the investigative process, one could administer ginseng to animals in the laboratory and observe its effect on known risk factors. Researchers in China, Korea, and Japan carried out numerous laboratory animal experiments showing that ginseng could lower blood cholesterol and lipids as well as blood sugar-the key elements in the blood that were the primary focus to determine the risk of developing cardiovascular disease. Those studies led to a continuing investigation in several countries and to human clinical trials.

In order to determine the potential of a pharmacology study to predict a corresponding clinical outcome, one must translate the laboratory dosage to the clinical dosage. The pharmacology experiments with ginseng that helped animals' survival under stress and that reduced risk factors associated with cardiovascular disease appear to support the dosage of ginseng recommended in the Chinese literature. Most of the studies on laboratory animals conducted in China, Korea, and Japan were based on doses of ginseng in the range of 25 mg/kg of bodyweight to 250 mg/kg (17, 18), though higher doses, such as 400 mg/kg, have occasionally been used in tests (e.g., for immune stimulation purposes). It is quite difficult to convert dosages in laboratory animals to those that would be used in humans, but with proper study design and analysis of factors influencing pharmacokinetics, it is possible to estimate what might happen in humans. A detailed analysis of conversion factors for such laboratory studies to human clinical applications was carried out by J. Boik (33). He indicates that the 25-250 mg/kg dosage range in mice corresponds to about 1-9 grams of ginseng for human use and that laboratory studies of ginseng for inhibiting cancer growth utilize amounts corresponding to a human dosage of 3.2-47 grams per day. The amounts of herb material used in the pharmacology testing for ginseng are similar to the amounts used in pharmacology tests of other Chinese herbs that, like ginseng, are administered to humans in doses of 3-9 grams per day in traditional practices. (11)

In addition to pharmacology studies that indicate reduction in factors associated with risk of heart disease, there have been investigations indicating that ginseng administration in animals improves immune functions, reduces stress-induced ulceration, provides antioxidant effects, inhibits tumor formation, and improves oxygen utilization (18). These diverse beneficial effects of ginseng were noted to be similar to those being reported at the same time for vitamin E (36). Thus, while ginseng appears to be confirmed by pharmacology studies as valuable to health, it is not necessarily more interesting or more potent than vitamin supplements. In fact, one result of the research into ginseng effects was the production of nutritional supplements with ginseng added with the hope of improving upon the benefits of each component.

Despite the extensive research efforts, ginseng was not accepted by the modern medical profession outside of Asia as a remedy for these health issues. It is not surprising, then, that the Western ginseng market shifted focus to a different area of concern.

GINSENG AND ENERGY: A NEW TWIST

The Chinese term qi, which has a rich meaning in the Chinese culture (see: Drawing a Concept: Qi), was translated by some Westerners simply as "energy." The concept of tonifying qi in the Chinese medical system was depicted, inaccurately, as stimulating energy. In other words, when a person was feeling run down, instead of, or in addition to, taking a cup of coffee, one could take ginseng, a qi-tonifying herb, in order to feel some immediate energy. In her book Asian Health Secrets (54), Letha Hadady described the situation this way: "Most Westerners use Chinese ginseng like jet fuel, to drive themselves beyond their capacity."

The claim that ginseng increases energy has become the lead concept in ginseng marketing. Today's functional foods (e.g., beverages spiked with vitamins, amino acids, and/or herbs) include ginseng in the category of "energy products," and ginseng is found in many of the herbal capsules, tablets, or liquid preparations aimed at improving energy. Ephedra, or ma-huang (Ephedra sinica), with its potent alkaloids, has been promoted in the same way for this purpose (typically at a dose of 20-25 mg ephedrine alkaloids each dose, up to three or more times per day). In an effort to get an energy boost from herbs, people have sometimes used extreme amounts or unusual combinations of herbs. One result can be adverse reactions and, as can be seen with the current calls for restrictions, negative publicity and fear.

For example, a "ginseng abuse syndrome" was described in a highly controversial report published in 1979 (13). Although the validity of this syndrome was later challenged (14), it remains a caution that is often raised about ginseng, regardless of the amount to be consumed. For the most part, the adverse reactions attributed to excessive use of ginseng, as conveyed in the 1979 article, may have been due to other products also used in excess at the same time (including high levels of caffeine). Some people, however, consumed unusually large amounts of ginseng to get an immediate reaction and this may have generated adverse effects, especially with prolonged overdosing.

The late Israel I. Brekhman, the Russian proponent of using herbs such as ginseng as adaptogens, described ginseng as having a stimulant action, and Russian researchers responded by focusing on this potential application (22). By contrast, Chinese researchers insisted that ginseng functioned as a mild sedative and calming agent; the ability to overcome fatigue, for example, was described as the result of having less stress on the body rather than by causing an overt stimulation. One peculiar effort to resolve the differences in these viewpoints was made by a Japanese researcher, Hiroshi Saito, who suggested that ginseng did both: some of the ginsenosides, particularly the R_g series, were stimulating in nature while others, particularly the R_b series, were calming in nature (56). He and co-worker Yien-mei Lee, pointed out that "We noticed that multiple pharmacodynamic activities of ginseng originated from various ingredients and there are many pharmacologically antagonistic actions in ginseng." How these apparently competing effects of some active components could explain away the difference of opinion about ginseng effects when ginseng was used as a whole preparation and not subdivided was never made clear by any subsequent authors who used the underlying concept in the attempt to cover-up incompatible claims.

As an example of the confusion generated by those making claims for ginseng's effect on energy, it has been suggested that Asian ginseng is "stimulating," but that American ginseng is "calming." One origin of this concept may be traced to the Chinese view regarding yin and yang. In China, it has been said that Chinese ginseng has the ability to tonify qi and invigorate yang [corresponding roughly to metabolism and movement], while American ginseng has the ability to tonify qi and nourish yin [corresponding roughly to control and calming]. However, this analysis comes about from a peculiar historical situation rather than an inherent difference in the herbs. Chinese ginseng comes from the far north of China; American ginseng was always imported through Canton, in the far south. From this experience, the Chinese had viewed their own ginseng as a northern product and the American ginseng as a southern product. In fact, American ginseng is obtained mainly from the northern part of the eastern U.S. and Canada, regions that are geographically similar to the part of China from which Asian ginseng is obtained.

The north, being cold, would yield, by ancient dogma, a product that benefits yang; the south, being warm, would yield a version of the same herb that benefits yin. Although, to this day, American ginseng is classified among the yin nourishing herbs in some Chinese herb guides, it is not described as more calming than the Chinese species, which is already depicted as having a calming action. American ginseng is sometimes said to be more cooling, however, and useful in tea for the sweltering summer heat of southern China.

To quote from one Chinese herb guide detailing the uses and applications of American ginseng (15): "Traditional uses: nourishes yin, cleanses heat, increases salivation, supplements the lungs, moistens, and depresses fire. Applications: heat symptom-complex, pulmonary tuberculosis, dry cough due to deficiency heat." Ignoring the historical origins of the different concepts about American and Asian ginseng, those who discuss the energizing or calming effects suggest that the difference involves the precise mix or ratio of ginsenosides. At this time, there is no evidence to support the contention that the mix of ginsenosides, at the dosage ingested, has any significant influence on the effect of ginseng. There have been no valid measures for stimulant properties of ginseng as applied to humans and there have been no comparative studies of the clinical effects of the different species of herbs sold as ginseng. One cannot say with scientific certainty whether one species is better, worse, or different in effect from the others, though it is possible to assay the total amount of ginsenosides. There is no substantive evidence that any difference in proportions of ginsenoside subsets between Asian and American species produces any difference in clinical effect of consuming the roots.

CHALLENGES ARISING WITH GINSENG PRODUCTS AND THEIR USE

Disturbing reports began to surface in the late 1970s and have been repeated several times since, that some ginseng products didn't contain ginseng or contained only weak or inactive ginseng, as had been suspected by ginseng experts for many years. Tests were developed to evaluate commercial products for ginsenoside content, which was found to vary considerably (19). In the first such study, conducted by researchers at the Philadelphia College of Pharmacy and Science, some of the commercial products analyzed contained so-called "Siberian ginseng," an herb that was being promoted initially by the Soviet Union and later by China. It was derived from eleuthero (Eleutherococcus senticosus), which contains no ginsenosides. In a Swiss study reported at a Chinese medicine conference in 1984 (58), six Asian ginseng products were evaluated and found to contain from as little as 0.3 mg ginsenosides per dosage unit (capsule) to 27 mg of ginsenoside per dosage unit (ampoule of ginseng extract), a 90-fold range.

Finn Sandberg, a Swedish ginseng researcher, described the situation with product variability this way, in response to questions about the validity of ginseng clinical test results (31): "Does [the favorable clinical test result] apply to other ginseng preparations? From a strictly scientific point of view, it is valid only for that particular batch of capsules that was used; but it will certainly be valid for other batches of capsules, provided they have an identical composition. Here comes the problem!" Such concerns about the variability of ginseng used for both testing and for commercial products led to promotion of what has been called "standardized ginseng." Standardized ginseng has different meanings for different manufacturers, some have used the term loosely, such as when simple steps have been taken to assure that the product meets a certain level in terms of amount of ginseng in the product or the amount of total ginsenosides in the product.

The first product referred to as a "standardized ginseng" was called G115 (21, 22). The manufacturer of G115 (Pharmaton, Lugano, Switzerland) has not described its processing method, but has claimed to provide 100 mg of the ginseng extract in a capsule, with 4% total ginsenosides. As described in a review article on ginseng (27): "Each capsule of G115 contains 100 mg of a concentrated aqueous extract of P. ginseng, which is titrated, that is, diluted, at 4% ginsenosides and equivalent to 500 mg P. ginseng root." Recent testing of samples (61), indicated that recent batches of this product barely contained the claimed amount, sometimes falling short.

The meaning of standardization developed by this company (which also produces a capsule titrated to 7% ginsenosides) appears to be two-fold: that both the amount of ginseng extract in a capsule and its percentage of total ginsenosides are set at a certain level. However, no consistent definition of standards for such products has been utilized by the herb industry, although the American Herbal Products Association has recently developed definitions recommended to the industry. One effect of the standardization is that it became a requisite of many Western studies to utilize standardized ginseng. A certain confidence in the value of the studies using standardized ginseng has evolved because the ginseng was well-defined.

Such confidence is sometimes misplaced. Thus, for example, in the book Herbal Prescriptions for Better Health (50), the author, a naturopathic physician, states that: "The best researched form of ginseng is extracts supplying approximately 4 to 7 percent ginsenosides. The recommended dosage is 100 milligrams once or twice daily. Crude non-standardized extracts require a higher daily dose of 1 to 2 grams." In fact, the standardized ginseng extracts mentioned here are the most frequently researched of the commercial extracts (here, he doesn't mention the brand but clearly means the Pharmaton product), but not necessarily the best researched in terms of quality of the studies. There is no evidence whatsoever that other non-standardized extracts need to be used in doses that are 10 times higher. The author's implication is that by standardizing the extract it becomes far more potent than other extracts, which is unproven and unlikely.

By gaining confidence in standardized material administered in trials, readers may ignore other potential weaknesses or flaws in the design and reporting of the studies. In a review of ginseng's potential for affecting sports performance (37), much of which relied on using the standardized ginseng preparations of Pharmaton, the authors comment that: "The published literature was characterized by numerous statistical and design problems. Much of this research failed to control for various behavioral artifacts...." They found that "there is an absence of compelling research evidence regarding the efficacy of ginseng use for the purpose of improving physical performance in humans." Similarly, in a review and meta-analysis British researchers (32) concluded that "...there is compelling evidence for none of the claimed indications."

One of the design flaws that was not mentioned in the reviews of ginseng trials was the low dosage of ginseng administered, levels that do not make sense from the perspective of modern knowledge of herbal pharmacology. If European ginseng research repeatedly underdoses the ginseng, then no other design characteristic will overcome this fundamental flaw.

SHRINKING DOSAGE RECOMMENDATIONS AND EUROPEAN RESEARCH

While in China the recommended dosage of ginseng for medicinal purposes has been consistent from ancient times up to the present (at several grams per day), the amount of ginseng suggested to be taken in the West has become relatively miniscule. Recommended doses of standardized ginseng products are typically one capsule each time. For the most frequently cited 4% ginsenoside extract in capsule form, the daily dose of ginseng extract is just 200 mg, and the daily amount of ginsenosides is just 8 mg. This 8 mg of ginsenosides is said to be derived from 1 gram of ginseng, which is the lowest daily ginseng dosage recommended in any Chinese texts, and corresponds to an extremely weak ginseng root (with 0.8% ginsenoside content rather than more typical levels that are at least twice that high).

By contrast, clinical work in Asia is carried out with far higher amounts of ginseng and for uses that differ markedly from those described in the West. The Pharmacopoeia of the People's Republic of China (16) officially lists 3-9 grams as the dosage for ginseng in decoction (tea) form. Thus, for example, in the attempt to prevent and treat cardiovascular diseases, ginseng is given in this dosage range to lower blood pressure. By contrast, Western literature cautions persons with hypertension to avoid ginseng, especially to avoid red ginseng, even in the much lower doses used in the West. In a recent report from Korea (20), red ginseng was administered at a dose of 4.5 grams per day (Korean red ginseng powder, 1.5 grams per dose, three times daily) and reported to have a slight blood pressure lowering effect (about 5% average decline) after two months daily administration. In reviewing prior studies of ginseng's effect on hypertension, the authors of that study noted that there had been negligible or minor effects on blood pressure previously mentioned for administration of 3 grams red ginseng powder every day for three months and with 3-6 grams of red ginseng powder every day for an average duration of 10 months.

As a reflection of this direction in ginseng research, in 1980 the Institute for Traditional Medicine of Portland, Oregon conducted a clinical trial in Santa Cruz, California on the impact of Asian ginseng on the risk factors for cardiovascular disease: cholesterol, triglycerides, elevated blood sugar, and blood pressure (23). In that study, the first clinical trial of ginseng in the U.S., 100 patients received red ginseng provided by the Korean Ginseng Research Institute at a dosage of either 3.0 or 4.5 grams per day (others received a placebo). Only modest effects were observed after three weeks of daily administration of the ginseng capsules, with slight favorable improvements in the risk factor measurements.

Two recent Chinese clinical trials made use of closely-related ginseng formulations-ginseng plus tienchi ginseng (sanqi) with amber (26), and ginseng plus tienchi ginseng and rhubarb root (27)-for treatment of angina pectoris and coronary heart disease, respectively. In the first study, the herbs were powdered and administered at the dose of 3 grams, three times daily. The total amount of ginseng (P. ginseng plus P. pseudoginseng) ingested by the patients each day was 7.2 grams. The treatment time was 12 weeks. The study report indicated that there were beneficial effects of the treatment and no adverse responses were noted. In the second study, the P. ginseng was a water-based extract, while the P. pseudoginseng was used as a powder (as is routine practice for this herb). The daily dose of the preparation administered was 2.4 grams, with 1.9 grams of it being a combination of the extract and powder of ginseng. Although the concentration of the extract was not stated, it is common to produce ginseng extracts that are about 4:1, meaning that the total dosage of ginseng crude materials used to make a daily dose in the treatment regimen would be about 5 grams. Again, benefits were claimed without report of adverse events during a treatment time of 3 weeks. These studies employed about 5-7 grams of ginseng, consistent with the Chinese Pharmacopoeia recommendation of 3-9 grams.

Even in the treatment of infants, high doses of ginseng are recommended in China. Gu Chifan described the use of ginseng for newborn babies (38):

The usual dosage is 3 grams a day. For infants of low birth weight or neonates within 1-2 days after delivery, reduce to 2 grams a day, as a drink or nasal feeding the steamed juice of red ginseng. Giving higher dosage is not necessary. Side effects such as tachycardia will appear if the dose is over 6 grams a day. Some individuals manifest slight diarrhea or rash after administration for 3 days, but it will disappear spontaneously after discontinuance.

An increasing number of European reports of ginseng effects based on small amounts of standardized ginseng appear in the literature, yet there are a few researchers using quantities comparable to those used in Asia. For example, a Canadian study investigating the reported blood sugar lowering effects of ginseng involved administration of 3 grams of American ginseng (41). The authors commented, "In our study, we noticed our effect with a high dose (3 grams) relative to that given by others studying various types of ginseng in humans. A review of clinical studies shows that the quantity administered is typically 1.5 grams or less."

In the clinical reports from Asia cited above, the ginsenoside content of the ginseng root material used is not specified. Separate studies conducted in Asia reveal typical levels of ginsenosides of about 4%, while Western studies indicate lower amounts, such as 1.5-2.0%. However, whether one uses the figure of 1.5% ginsenoside content for ginseng roots as the specified minimum in Europe, or uses the higher level reported in Asian sources, the doses of ginseng cited in these clinical reports correspond to from 45-135 mg (at 1.5%) to 120-360 mg (at 4%) of the saponin components. This is in marked contrast to recommendations for use of standardized ginseng products at doses of just 8-14 mg/day of ginsenosides.

There are only a few studies conducted in Asia in which isolated ginsenosides are given clinically. In a Chinese study (42), the saponins isolated from P. ginseng fruits were administered to 327 patients aged 50-70 to test the saponins' antisenility actions. The dosage administered was 150 mg/day. A similar clinical study was conducted with saponins isolated from P. ginseng rhizome: 358 patients aged 50-85 were given 150 mg/day of the saponins (50 mg each time, three times a day) for two months (51). Prolonged administration of the saponins for up to two years showed no adverse side effects. In a Korean study (43), ginsenosides of the triol series (e.g., ginsenosides of the G series, as in R_g1 etc.) were given to 120 patients who had gone through gynecological laparotomies, in an attempt to aid recovery. The dosage administered was 230 mg/day. These doses of isolated saponins are consistent with the amounts expected to be obtained from the ginseng powder and crude extracts in those studies cited above, but are more than 10 times higher than the saponin levels administered in Europe with the commonly used standardized ginseng capsules.

When using Panax ginseng, the consumer would generally prefer to take relatively few capsules or tablets. In fact, it is not difficult to ingest the higher levels of ginseng or its ginsenosides, at least if one can obtain high quality ginseng roots. Ginseng root powder at 500 mg per capsule will provide 3 grams of ginseng in just six capsules (e.g., three capsules, two times per day). In addition, ginsenoside-rich extracts from P. ginseng are prepared in China with 20-85% ginsenosides, making it easy to get a desired amount of ginsenosides into a single capsule. To get the higher ginsenoside concentrations, ginseng leaves and/or fruits are used as a source material. Ginseng fruits are especially rich in ginsenoside Re, which was shown to have antidiabetic activity, similar to that of the other ginsenosides (28). These concentrated ginsenoside extracts have been subjected to clinical evaluations in China, particularly for elderly patients who may have trouble consuming large amounts of capsules or tablets, and deemed an effective substitute for crude powders (42).

SUMMARY AND CONCLUDING REMARKS

This article has reviewed the traditional understanding and uses of Asian ginseng (Panax ginseng), its usual recommended dosage, the type and levels of active constituents found in ginseng, and the complex situation surrounding modern research efforts. The information presented here suggests that:

• The traditional uses of ginseng primarily revolve around promoting digestive system functions, improving nutrition, and calming agitation; the modern applications in Asia are particularly aimed at preventing and treating cardiovascular diseases and problems of aging, including diabetes. By contrast, ginseng is often described today in the West as an energizing agent, a stimulant that is a healthy substitute for caffeine, though caffeine has not been shown to be harmful in normal use.
• The usual recommended dosage of ginseng in Asia is most often in the range of 3-9 grams/day. By contrast, herb product manufacturers in the West may recommend using far less, with amounts that are of questionable potential to provide any of the desired ginseng actions.
• The primary active constituents in various species of Panax are saponins called ginsenosides. European researchers report lower levels in the roots than their Asian counterparts. The concentrations also vary according to the species of ginseng and its method of preparation. Based on the Chinese recommendations for dosage of the roots-and for the dosage of isolated ginsenosides that are sometimes given in clinical studies-the amount of ginsenosides to be taken in one day would typically be about 80-240 mg for long-term administration (several weeks or months). European recommendations for dosage of the ginsenosides are much lower, by about a factor of 10, and don't correspond to the levels shown effective in most pharmacology studies.
• Modern research into ginseng and its effects has been hampered by poor quality in study design and reporting. As a result, many physicians and researchers do not find the effects that have been reported to have a credible basis. On a precautionary basis, the reports of adverse effects appear more acceptable to many well-trained physicians than reports of beneficial effects. The research efforts have largely focused on anti-fatigue actions and reduction of risk factors for cardiovascular diseases, though other areas of interest have been pursued (e.g., radioprotective and chemoprotective effects).

Ginseng has a long history of use in Asia that has generated interest in continuing the tradition into the present and studying, by modern methods, the constituents of ginseng and their pharmacological and clinical effects. A careful reading of both the traditional literature and modern Asian and Western research efforts is essential to help guide consumers and healthcare professionals towards knowing the correct indications and dosages for ginseng, selecting appropriate ginseng materials to use, and avoiding unsubstantiated claims of beneficial or harmful effects.

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August 2002