Ginseng, Asian

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Panax ginseng C.A. Meyer (syn. P. schinseng T. Nees)

[Fam. Araliaceae]

Overview

Asian ginseng is one of the most economically important medicinal herbs in world trade (Iqbal, 1993; Ma, 1999). In the U.S., ginseng ranks second in total sales in food, drug, and mass market retail stores with sales in 2000 totaling $62.5 million (Blumenthal, 2001). The U.S. Department of Commerce (USDOC) tracks ginseng imports due to the herb’s significant economic value. The U.S. imports over 1 million pounds of cultivated Asian ginseng roots annually mainly from China, Hong Kong, and Korea (USDOC, 2000). The quantity and value of finished ginseng consumer products imported into the U.S. from Europe and Asia are significant. In Germany, ginseng is one of the few economically important herbal drugs listed separately in the Foreign Trade Statistics. A considerable amount of ginseng is value-added (i.e., processed into finished products) in Germany, and then exported mostly to France, Italy, and Argentina (Lange and Schippmann, 1997). A recent study by the American Botanical Council’s Ginseng Evaluation Program, found that the quality control regarding standardized ginseng products was reasonably consistent over five separate lots of 13 different products (Hall et al., 2001).

Asian ginseng (Panax ginseng) is indigenous to northern mountainous regions of China and Korea and far eastern regions of the Russian Federation (Blumenthal et al., 2000). Though Asian ginseng is cultivated in China, Japan, Korea and Russia (Siberia), the Republic of Korea, and China are the main producers and exporters of the herb (Iqbal, 1993).

In Asia, the medical use of ginseng dates back thousands of years, though the first written account of its use appears in Shen-nung pen-ts’ao-ching, the first Chinese Materia Medica, believed to have been compiled during the Late Han Dynasty in the first century C.E. (Hu, 1977). Ginseng has remained an important medicine in the health care systems of China, Japan, and Korea (JSHM, 1993; PPRC, 1997). Asian ginseng has also become integrated into European medicine (Morant and Ruppanner, 2001; Blumenthal et al., 2000; DAB, 1999; ÖAB, 1990; Ph.Eur., 2001). In Sweden, ginseng represents the top-selling category of all registered natural remedies (Tunón, 1999). An extensive review of the detailed chemistry, mechanisms of action, pharmacology, therapeutics, and related information on P. ginseng was recently published, stating that since 1960 more than 4,000 research articles have been published in the scientific literature covering Asian ginseng (Court, 2000). Another review has focused on the ginsenosides, the primary active constituents, and includes biological effects noted in pharmacological and clinical studies on ginsenosides from ginseng root and aerial parts (leaves, flowers, fruits) (Chen et al., 2002).

Description

White ginseng root (also referred to in the literature by its pharmaceutical name, Radix Ginseng) consists of the mature dried root of Panax ginseng C.A. Meyer [Fam. Araliaceae], collected in autumn and dried in the sun (PPRC, 1997). Before drying, the root is washed, and the rhizomes are removed (JSHM, 1993). White ginseng root contains no less than 0.4% of combined ginsenosides Rg1 and Rb1, calculated with reference to the dried root (Ph.Eur., 2001), or no less than 1.5% of total ginsenosides calculated as ginsenoside Rg1 (Blumenthal et al., 1998; DAB, 1999). Red ginseng root (Radix Ginseng Rubra) is produced by steaming the raw root at 98–100°C for two to three hours (Kim et al., 2000), then drying. The concentration of the major ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, Rgl) are slightly higher in white ginseng than red ginseng (Yun, 1996).

Primary Uses

Adaptogen and general tonic (Amato et al., 2000; Court, 2000)

Fatigue and physical performance

Increased athletic performance and endurance (Le Gal, 1996; Van Schepdael, 1993; Cherdrungsi and Rungroeng, 1995), (although several more recent studies have not resulted in positive outcomes for performance enhancement [Bahrke and Morgan, 1994, 2000])

Immunology

Immunomodulatory effects (Scaglione et al., 1990, 1996; Srisurapanon et al., 1997)

Other Potential Uses

Diabetes

Non-insulin dependent diabetes mellitus (Sotaniemi et al., 1995)

Gynecology

Menopausal symptoms (Wickland et al., 1994; Reinold 1990)

Male Reproductive Health

Aphrodisiac (Amato et al., 2000); erectile dysfunction and fertility (Salvati et al., 1996; Choi et al., 1995)

Mental Health

Improved cognitive function and mental performance (Sørenson et al., 1996; Smith et al., 1995; Rosenfeld, 1989; Von Ardenne et al., 1987; D’Angelo et al., 1986; Fulder et al., 1984; Dorling, 1980; Johnson et al., 1980), although the effects on psychological well-being in normal healthy young adults were not confirmed in a later study (Cardinal and Engels, 2001).

Oncology

Possible reduction of risk of gastric cancer, as well as cancer of the, lungs, ovaries, larynx, esophagus, and pancreas (Kakizoe, 2000; Yun and Choi,1998; Yun and Choi, 1995; Yun and Choi, 1990)

Maintained CD4+ T-cell counts and delayed resistance to zidovudine in HIV + patients taking Korean red ginseng combined with zidovudine (Cho et al., 2001).

Respiratory System

Improved pulmonary function in treatment of severe, chronic respiratory disease (Gross et al., 1995); additive effect of antibiotic treatment for respiratory tract infection (Scaglione et al., 2001, 1994)

Ginseng root extracts and/or isolated ginsenosides have been studied clinically for the following indications with some positive results: general quality of life, adaptogenic activity and physical stress, anti-aging effects, aphrodisiac effects, memory and intellectual skills, diabetes, various types of cancers, angiocardiopathy and other cardiovascular parameters, hepatitis, peptic ulcer, aplastic anemia, atherosclerosis, and others (Court, 2000; Chen et al., 2003).

Traditional Chinese Medicine (TCM) Indications

White Ginseng (Renshen)

Prostration with impending collapse marked by cold limbs and faint pulse; diminished function of the spleen with loss of appetite; cough and dyspnea due to diminished function of the lung; thirst due to impairment of body fluid; diabetes caused by internal heat; general weakness with irritability and insomnia in chronic diseases; impotence or frigidity; heart failure and cardiogenic shock (PPRC, 1997).

Red Ginseng (Hongshen)

Collapse tendency due to asthenia; cool limbs and weak pulse; qi (vital force) cannot control blood; uterine bleeding; cardiac failure and cardiogenic shock (PPRC, 1997).

Note: In TCM, the terms “spleen” and “lung” do not correlate to the Western system of anatomy, but are part of a system of classification defined by their functions and relationships. Also, in TCM, herbs are rarely used as monopreparations and almost always used in combinations (Kaptchuk, 1983); it is therefore difficult to attribute the traditional uses of ginseng to the pharmacology of this herb alone as the actions of other herbs used in classic formulas may have an additive or synergistic effect.

Dosage

Internal

Crude Preparations

Dried root, powdered: 1–2 g daily for up to three months (Blumenthal et al., 1998).

Decoction: 3–9 g dried root simmered in 720–960 ml water for approximately 45 minutes (PPRC, 1997).

Infusion: 150–250 ml boiling water poured over 1–2 g fine cut or powdered root, steeped covered for 10 minutes, then strained (Blumenthal et al., 1998, 2000).

Fluid extract: 1:2 (g/ml): 1–6 ml daily (Bone, 1998).

Note: The German Commission E specifies cut root for teas, powder, or equivalent preparations (Blumenthal et al., 1998). In an infusion of coarsely powdered root, the yield of total ginsenosides at 10 minutes steeping time is 64%, and the yield is 73% at 15 minutes. If decocted, the yield of ginsenosides is 69% at 5 minutes and 77% at 15 minutes. A cold maceration will yield 71% at 60 minutes (Meyer-Buchtela, 1999).

Standardized Preparations

Dry extract: Standardized to 4% ginsenosides, 2x100 mg capsules daily taken with liquid at breakfast, or 1 capsule with breakfast and 1 capsule with lunch (Morant and Ruppanner, 2001). Note: Much of the pharmacological and clinical research conducted on the leading 4% standardized ginseng extract (G115^®) suggests that 200 mg of this extract, yielding 8 mg ginsenosides per day, is an optimal dose (Soldati, 2000). However, a review of historical literature and recent pharmacological investigations conducted in Asia suggests that significantly higher doses (3–9 g of dried root, equivalent to as much as 80–240 mg ginsenosides per day) are possibly warranted (Dharmananda, 2002).

Duration of Administration

According to the German Commission E, ginseng can generally be used up to three months, with a repeated course of treatment possible (Blumenthal et al., 1998).

Chemistry

Ginseng root contains up to 40 dammarane- and oleanane-type saponins, polyacetylene derivatives, and polysaccharides (Chen et al., 2003; Court, 2000; Fukuda et al., 2000; Tang and Eisenbrand, 1992). Saponins are believed to be the primary active components of ginseng, with characteristic dammarane-type saponins divided into two major groups based on their aglycones; (1) 20(S)-protopanaxadial: ginsenosides Rb1, Rb2, Rc, and Rd; and (2) 20(S)-protopanaxatriol: ginsenosides Re, Rf, Rg1, and Rg2 (Kwon et al., 2000). Ginsenoside Ro is an oleanane-type saponin (WHO, 1999). Ginseng also contains alkaloids, phenols, amino acids, polypeptides, proteins, and other constituents (Court, 2000).

Raw (white) ginseng root contains 0.56–0.95% ginsenoside Rb1, 0.52–0.74% ginsenoside Rb2, 0.48–0.72% ginsenoside Rc, 0.26–0.46% ginsenoside Rd, 0.38–0.64% ginsenoside Re, 0.11% ginsenoside Rf, 0.39–0.61% ginsenoside Rg1 and 0.13% ginsenoside Rg2 (Chuang et al., 1995; Kim et al., 2000; Kwon et al., 2000) 0.005% volatile oil (Yen, 1992).

Steamed (red) ginseng root, depending on the temperature used during steaming, contains 0.12–0.5% ginsenoside Rb1, 0.1–0.44% ginsenoside Rb2, 0.17–0.57% ginsenoside Rc, 0.14–0.27% ginsenoside Rd, 0.02–0.3% ginsenoside Re, 0.1–0.12% ginsenoside Rf, 0.22–0.35% ginsenoside Rg1, 0.2–0.3% ginsenoside Rg2, 0.24–1.32% ginsenoside Rg3, 0.15–0.64% ginsenoside Rg5, 0.14–0.23% ginsenoside F4 (Kim et al., 2000). Ginsenosides Rg3, Rg5, and F4, do not occur in white ginseng and are formed as a product of the steaming process.

A high-performance liquid chromotography-tandem mass spectrometry method was developed to distinguish between P. ginseng (Asian ginseng) and P. quinquefolius (American ginseng). This method differentiates between American ginseng containing 24(R)-pseudoginsenoside F11 in excess of 0.1% (w/w) in the dried root and Asian ginseng containing trace levels of less than 0.00001% (Wenkui et al., 2000).

Ginsenosides are quite stable: They were identified in 1,200 year-old root samples from Japan (Court, 2000).

Pharmacological Actions

Pharmacological studies on Asian ginseng are numerous and are summarized in recent publications (Chen et al., 2003; Court, 2000; Tang and Eisenbrand, 1992).

Human

Red ginseng root

Demonstrated a long-term, immunomodulating effect in human immunodeficiency virus (HIV) patients (Cho et al., 1997); improved parameters of rigidity and tumescence in erection, early detumescence, libido, and satisfaction (Choi et al, 1995).

Standardized extract

Increased natural killer cell activity (Scaglione et al., 1996); showed significant immunomodulatory effects (Scaglione et al., 1990); reduced plasma total cholesterol and triglycerides, and elevated HDL levels (Yamamoto et al., 1983).

Powdered root

Significantly increased mean platelet count (Chang et al., 1980).

Animal

Increased resistance in coldness test and immobilization test in rodents (Blumenthal et al., 1998); increased oxidative capacity of the skeletal muscle in rats (standardized extract) (Ferrando et al., 1999); demonstrated hormone-like and cholesterol-lowering effects, promoted vasodilation, acted as anxiolytic, and antidepressant (Choi et al., 1995; Chong et al., 1988); prevented cancer-causing effects of DMBA, uerethane, and aflatoxin in newborn mice (Yun et al., 1993); inhibited alcohol-induced amnesia in rats (Lee et al., 2000); enhanced thermogenic capacity (Wang and Lee, 2000); enhanced energy metabolism (Avakian et al., 1984); protected against irradiation damage (Takeda et al., 1981, 1982); reduced injuries and inflammation caused by eccentric muscle contractions in rats (de Oliveira et al., 2001); Ginseng Total Saponin (GTS) fraction inhibited striatal dopamine release stimulated by local infusion of nicotine in male rats (Shim et al., 2000).

In vitro

Anti-tumor: Isolated ginsenoside Rg3 demonstrated anti-
proliferation activity in human prostate cancer cell line (Liu et al., 2000); isolated ginsenosides have shown antitumor effects in human and mouse tumor cells (Molnar et al., 2000).

Broncho-relaxing: Ginsenosides induced relaxation of human bronchial smooth muscle via stimuation of nitric oxide generation, mainly from airway epithelium and cyclic GMP synthesis, possibly explaining the anti-asthmatic effect of ginseng (Kawatani et al., 2000).

Traditional Chinese Medicine (TCM) Actions

According to the concepts inherent in TCM, the actions of ginseng are explained in terms of TCM’s energetics model as follows:

White Ginseng (Renshen)

Reinforces vital energy (qi), remedies collapse and restores normal pulse, benefits the spleen and lung, promotes production of body fluid, calms the nerves (PPRC, 1997). Note: “spleen” in TCM is not the specific anatomical organ known in Western medicine; in TCM, “organs” are discussed with reference to their functions and relationships to other organs, substances and other body parts. In most cases, the term “spleen” in TCM refers to the entire digestive system.

Red Ginseng (Hongshen)

Replenishes vital essence (jing), promotes blood circulation and relieves collapse, reinforces qi and stanches bleeding (PPRC, 1997).

Mechanism of Action

Some research suggests that ginseng acts through both the hypothalamus-pituitary-adrenal axis and partly through its immunomodulatory activity (WHO, 1999).

In vitro, isolated ginsenosides have shown a chemical structure-dependent immunomodulating effect by enhancing the activity of natural killer cells and ADCC (antibody-dependent cell-mediated cytotoxicity) activities, the effect being structure-dependent (Molnar et al., 2000).

For male impotence, ginseng saponins appear to depress blood prolactin levels, causing increased libido (WHO, 1999), suggesting that ginseng may have an effect at different levels of the hypothalamus-pituitary-testes axis (Salvati et al., 1996).

Based on animal experiments, pretreatment with either ginseng extract or its isolated saponins block
methamphetamine- or cocaine-induced behavioral activity. Ginseng Total Saponins (GTS) inhibits striatal dopamine release stimulated by local infusion of nicotine, suggesting that ginseng may act on presynaptic nicotinic acetylcholine receptors (nAChRs), or receptor-operated Na+ channels in dopaminergic nerve terminals, though not on voltage-sensitive ion channels (Shim et al., 2000).

Red ginseng total saponin’s (RGTS) inhibition of alcohol-induced amnesia in rats is dependent on catecholaminergic but not serotonergic neuronal activity (Lee et al., 2000).

Depressant and stimulant effects on the central nervous system by the two main ginsenosides, Rb1 and Rg1, (Chong and Oberholzer, 1988) indicate that the pharmacological actions of individual ginsenosides may work in opposition. In rats with selective hippocampal lesions, red ginseng amelioriates learning and memory deficits through its effect on the CNS which may be partly due to its effects on hippocampal formation (Zhong et al., 2000).

Contraindications

The Commission E and World Health Organization (WHO) report that there are no known contraindications for Asian ginseng (Blumenthal et al., 1998; WHO, 1999). The British Herbal Compendium (BHC) contraindicates ginseng in acute illnesses, hypertension, and with use of stimulants, particularly caffeine-containing beverages (Bradley, 1992).

Pregnancy and Lactation: No known restrictions are noted by the American Herbal Products Association (McGuffin et al., 1997) and the Commission E (Blumenthal et al., 1998), but controlled, long-term safety studies have not been conducted. The BHC contraindicates ginseng in pregnancy. The WHO monograph states that the safety of ginseng use during pregnancy has not been established, but it has been shown that ginseng is not teratogenic in vivo (WHO, 1999). Note: In TCM, ginseng root is included in prescriptions given during pregnancy, labor, and postpartum (Hu, 1977).

Adverse Effects

There is some confusion about the relative safety of Asian ginseng in the scientific literature. After evaluating various reports published prior to 1991, the Commission E determined that there was not sufficient basis for supporting definitive adverse reactions, concluding that there were none known (Blumenthal et al., 1998). One paper suggests that the relative safety of ginseng is supported by the contention that the dose required to produce adverse effects is about 1,000 times the normal effective dose (Chandler, 1988).

The WHO states, “Various researchers who studied Radix Ginseng extracts using conventional toxicological methods in five different animal models reported no acute or chronic toxicity of the extract. On the basis of Radix ginseng’s long use, and the relative infrequency of significant demonstrable side-effects, it has been concluded that the use of Radix Ginseng is not associated with serious adverse effects if taken at the recommended dose” (WHO, 1999). The BHC states that “Numerous studies have confirmed the safety of Ginseng; no significant toxicity or drug interactions have been reported.” (Bradley, 1992). Another leading manual for professionals (Newall et al., 1996) cites a report from Japan in which Asian ginseng was administered to more than 500 people in the course of two studies with no adverse side effects reported. There is considerable difficulty in evaluating individual case reports on ginseng due to a lack of information on dose, duration, species of ginseng (reports sometimes inadequately refer to “ginseng” without citing the specific type or species) and other simultaneous medication (Newall et al., 1996).

Despite the relative safety of Asian ginseng, reports surface in the literature regarding potential adverse reactions. Many writers continue to uncritically cite an uncontrolled study (Siegel, 1979) in which 133 people reportedly using some form of “ginseng” (type or identity not determined) were studied for potential adverse reactions. About 10% (14) reported hypertension, nervousness, irritability, insomnia, morning diarrhea, and related symptoms, which the author labeled as the “Ginseng Abuse Syndrome” (GAS). All subjects reporting these symptoms were determined to have taken abnormally large amounts of “ginseng” (up to 15 g per day), many with concomitantly large levels of caffeine, prompting the author to suggest a potential ginseng-caffeine synergy. The study has been discredited for being uncontrolled, for not having confirmed the identity of the purported ginseng products ingested, and because most of the symptoms of GAS are also associated with consumption of large amounts of caffeine (Blumenthal, 1991).

Other adverse effects are reported. WHO cites two cases of mydriasis, disturbance in accommodation, and dizziness that were reported from ingestion of relatively large doses (3–9g) of an unspecified ginseng product (Lou et al., 1989). There is one report of vaginal bleeding resulting from the vaginal application of a “ginseng face cream” (Hopkins et al., 1988). The composition of the cream was not analyzed to determine the identity of the purported ginseng contents and what level of ginseng may have been present; it is probable that other cosmetic ingredients in the preparation, intended and approved for safety in facial dermal application, but not for mucous epithelia, were responsible. The WHO discusses reports suggesting potential estrogen-like effects in premenopausal and postmenopausal women after use of ginseng. Seven cases of mastalgia as well as increased libido in premenopausal women have been reported; however, subsequent pharmacological studies on a standardized ginseng extract suggest that there is no interaction of ginseng constituents with either cytosolic estrogen receptors isolated from mature rat uterus or progesterone receptors from human myometrium. Additionally, clinical studies on a standardized ginseng extract show that ginseng does not alter male and female hormone levels (WHO, 1999).

Drug Interactions

The Commission E reported none known (Blumenthal et al., 1998). The WHO monograph cites two cases of ginseng interaction with phenelzine, a monoamine oxidase inhibitor, although the clinical significance of this interaction has yet to be determined. Diabetic patients may need to adjust insulin dosage because ginseng may reduce blood glucose levels slightly (WHO, 1999). Positive synergistic effects of ginseng combined with zidovudine in HIV patients have been reported (Cho et al., 1994). There is one case report of an interaction with warfarin resulting in a subtherapeutic decrease in clotting time (International Normalization Ratio) (Morreale and Janetsky, 1997). However, in a recent study on rats, the pharmacokinetics and pharmacodynamics of warfarin were not significantly altered with the addition of a decoction of ginseng (2 g/kg), twice daily over five days (Zhou et al., 1999). The BHC cautions against using ginseng with stimulants, including excessive caffeine (Bradley, 1992). A freeze-dried hot water extract of ginseng reduced blood alcohol levels 35.2% 40 minutes after the last drink of alcohol (Brinker, 2001). Case reports and pharmacological studies suggest that ginseng saponins can alleviate some of the adverse effects of glucocorticoid drugs (e.g., prednisolone) without significantly compromising the anti-inflammatory effect of the drug (Chen et al., 2003). In a clinical study ginseng extract (100 mg 2x daily) increased bacterial clearance from lungs in acute attacks of chronic bronchitis when combined with amoxicillin and clavulanic acid more than when the antimicrobial drugs were used (Brinker, 2001).

Traditional Chinese Medicine (TCM) Drug Interactions

According to the Chinese Pharmacopoeia, ginseng is incompatible with the root and rhizome of hellebore (Veratrum nigrum and presumably other species of Veratrum); however, the nature of this incompatibility is not explained (PPRC, 1997). Note: Veratrum species are not found in herbal products in the North American market.

American Herbal Products Association (AHPA) Safety Rating

Class 2d: Contraindicated in hypertension (McGuffin et al., 1997).

Regulatory Status

Austria: Official in the Austrian Pharmacopoeia (ÖAB, 1990) (Meyer-Buchtela, 1999; Wichtl and Bisset, 1994).

Canada: Food, if no therapeutic claims are made, and New Drug if drug claims are made (HPB, 1993) except as per the Traditional Herbal Medicine (THM) Policy. Permitted as an over–the–counter (OTC) THM, if the claim(s) are supported by traditional references, requiring premarket authorization and assignment of a Drug Identification Number (DIN) (Health Canada, 1999). Also, permitted as an OTC homeopathic drug with premarket authorization and assignment of a DIN (Health Canada, 2001).

China: Both white and red (steamed) dried root are official drugs in the Pharmacopoeia of the People’s Republic of China (PPRC, 1997).

European Union: Dried root containing not less than (NLT) 0.4% of combined ginsenosides Rg1 and Rb1 is official in the European Pharmacopoeia (Ph.Eur., 2001). The homeopathic mother tincture and dilutions thereof are also allowed in veterinary medicinal products for all food-producing animal species (EMEA, 1999).

France: Official in the French Pharmacopoeia (Ph.Fr.X) (WHO, 1999). Traditional Herbal Medicine for self-medication with specific indications (Bradley, 1992; Goetz, 1999).

Germany: Dried root containing a minimum of 1.5% ginsenosides, official in the German Pharmacopoeia (DAB, 1999). Dried main and lateral root, and root hairs containing a minimum of 1.5% ginsenosides, used for preparation as tea, powder, or equivalent galenical preparations, is an approved nonprescription drug of the Commission E monographs (Blumenthal et al., 1998).

Japan: Dried root with rootlets removed is official in the Japanese Pharmacopoeia, and powdered root is official in the Japanese Herbal Medicine Codex (JSHM, 1993).

Republic of Korea: Quality standards for ginseng extracts are published in the Korean Food Standard Code (KMHW, 1999; Kwon et al., 2000; Lee et al., 1999), which maintains specific guidelines for manufacturing and for ginseng product approvals (KMHW, 2000). All herbal drugs must meet the requirements of the Korean Pharmacopoeia, the National Institute of Health, and the Ministry of Public Health and Social Affairs (WHO, 1998).

Russian Federation: Official in the State Pharmacopoeia of the Union of Soviet Socialist Republics (Ph USSR X) (Bradley, 1992; Reynolds et al., 1989).

Sweden: Classified as Natural Remedy for self-medication requiring advance application for marketing authorization. A Panax ginseng monograph is published in the Medical Products Agency (MPA) “Authorized Natural Remedies,” which lists five registered monopreparations (e.g., Gericomplex^® and Ginsana^®) with the approved indication: “Traditionally used as a tonic in case of decreased performance such as fatigue and sensation of weakness” (MPA, 1999 & 2001; Tunón, 1999). Food, if no therapeutic claims are made.

Switzerland: Official in the Swiss Pharmacopoeia (Ph.Helv.) (Meyer-Buchtela, 1999; WHO, 1999). Positive classification (List D) by the Interkantonale Konstrollstelle für Heilmittel, and corresponding sales Category D with sale limited to pharmacies and drugstores, without prescription (Morant and Ruppanner, 2001; Ruppanner and Schaefer, 2000; WHO, 1998).

U.K.: Entered in General Sale List, Table A (internal or external use) of Schedule 1 (subject to a full Product License) (GSL, 1994).

U.S.: Dietary supplement (USC, 1994). Asian ginseng root and powdered Asian ginseng root, powdered Asian Ginseng extract, and ginseng tablets are official in the U.S. National Formulary (USP, 2002). A monograph for Asian ginseng root, dry extract, in capsules is in development (USPC, 2000).

Clinical Review

More than 60 clinical studies on ginseng have been published with most using a dry extract (G115^®) standardized to 4% total ginsenosides at a daily dosage of 200 mg. Its drug-to-extract ratio is approximately 5:1 (w/w) so that 200 mg of extract corresponds to about 1 g of dried root (Bone, 1998).

Twenty-nine studies are outlined in the table, “Clinical Studies on Asian Ginseng,” including a total of 12,037 participants. All but five of these studies (Engels and Wirth, 1997; Engels et al., 1996; Srisurapanon et al., 1997; Sørenson et al., 1996; Smith et al., 1995) demonstrated positive effects for indications including cancer prevention, diabetes, immune support, fatigue, menopause, and circulation. The table includes 15 double-blind, placebo-controlled (DB, PC) studies. Five of these investigated the ergogenic and anti-fatigue effects of ginseng extract on physical performance (Cherdrungsi and Rungroeng, 1995; Engels et al., 1996; Engels and Wirth, 1997; Le Gal et al., 1996; Van Schepdael, 1993). Six DB, PC studies examined the effect of ginseng on psychological functions (D’Angelo et al., 1986; Dorling, 1980; Forgo et al., 1981; Fulder et al., 1984; Johnson et al., 1980; Sørenson et al., 1996). Ginseng’s immunomodulatory activity is the subject of three DB, PC studies (Scaglione et al., 1990, 1997; Srisurapanon et al., 1997). One DB, PC study investigated the effect of ginseng on newly diagnosed non-insulin-dependent diabetes (Sotaniemi et al., 1995). Ginseng’s effect on erectile dysfunction and fertility in men was the focus of two studies (Choi et al., 1995; Salavati et al., 1996).

A review in a popular newsletter has raised issues regarding the design and results of some of these studies (Schardt, 1999). A recent meta-analysis questioned the general effectiveness of Asian ginseng on physical performance in young, healthy volunteers (Vogler et al., 1999). The meta-analysis acknowledged that nine of the 16 clinical trials reviewed concluded the “ginseng” preparation used in the trials had a positive effect. However, this review has been criticized because the authors included five different types of “ginseng”: Asian, American, Japanese (P. japonicus), Vietnamese (P. vietnamensis) and eleuthero (also known as Siberian ginseng) (Eleutherococcus senticosus). Such reviews should focus on a homogeneous substance or in this case, one species of an herb, especially since the reviewers themselves acknowledged the chemical differences among the species (Hoegler, 2001a).

In another review (Bahrke and Morgan, 2000), researchers examined 16 clinical trials involving athletes and other healthy subjects who tested ginseng’s effect on exercise performance. Criticizing the current level of ginseng research, the review’s authors discussed statistical and design problems, and methodological problems such as inadequate sample size and lack of DB, PC paradigms. Studies were conducted on ginseng combined with other ingredients (e.g., herbs, vitamins), and in some cases did not specify dose, duration, or specific parameters of the ginseng preparation. The authors of this review concluded that future trials should rectify design flaws so that a reasonable conclusion can be made about the effect of ginseng on physical performance. Another paper suggests that increasing dosage levels to be consistent with those used historically in TCM and in recent pharmacological experiments in animals would produce more positive outcomes in clinical trials measuring the ergonomic and other activities of ginseng (Dharmananda, 2002).

Branded Products*

Dansk Droge Ginseng tablets: Dansk Droge A/S / Industrigrenen 10 / 2635 / Ishoj / Copenhagen / Denmark / Tel: +43-56-5656 / Fax: +43-56-5600. 100 mg or 200 mg ginseng root (ginseng composition not stated).

G115^®: Pharmaton Natural Health Products / P.O. Box 368 / Ridgefield, CT 06877 / U.S.A. / Tel: 800-451-6688 / Fax: 203-798-5771 / www.pharmaton.com / Email: askpharmaton@rdg.boehringer-ingelheim.com.

Gerimax^® Ginseng extract: Dansk Droge A/S / Industrigrenen 10 / 2635, Ishoj, Copenhagen / Denmark / Tel: +43-56-5656 / Fax: +43-56-5600. Internal composition of tablet not disclosed in study.

Ginsana^® G115 capsules: Pharmaton Natural Health Products. One capsule contains 100 mg of standardized (4% total ginsenosides) ginseng root extract G115^®. Dry extract is approximately 5:1 (w/w) so that 200 mg extract corresponds to about 1 g of dried root.

Pharmaton^® capsules: Pharmaton Natural Health Products. One capsule contains 40 mg of standardized (4% total ginsenosides) ginseng root extract G115^®, 26 mg dimethyl aminoethanol bitartrate, 4,000 I.U. vitamin A, 2 mg vitamin B1, 2 mg vitamin B2, 1 mg vitamin B6, 1 mcg vitamin B12, 60 mg vitamin C, 400 I.U. vitamin D, 10 mg vitamin E, 15 mg niacinamide, 2.8 mg copper sulphate monohydrate, 3.1 mg manganese sulphate monohydrate.

PKC 167/79: Pharmaton S.A. / CH-6903 / Lugano / Switzerland / Tel: +41-91-610-3111. Each capsule contains 100 mg of ginseng extract derived from an aqueous solution. Investigational product only, not available.

*American equivalents, if any, are found in the Product Table beginning on page 398.

References

Amato M, Izzo A, Nocerino E. The aphrodisiac and adaptogenic properties of ginseng. Fitoterapia 2000;71:S1-S5.

Ando T, Muraoka T, Yamasaki N, Okuda H. Preparation of antilipolytic substance from Panax ginseng. Planta Med 1980;38:18–23.

Avakian E, et al. Effect of Panax ginseng extract on energy metabolism during exercise in rats. Planta Med 1984;50:151–4.

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